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Antimicrobial peptides: an alternative for innovative medicines?

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Abstract

Antimicrobial peptides are small molecules with activity against bacteria, yeasts, fungi, viruses, bacteria, and even tumor cells that make these molecules attractive as therapeutic agents. Due to the alarming increase of antimicrobial resistance, interest in alternative antimicrobial agents has led to the exploitation of antimicrobial peptides, both synthetic and from natural sources. Thus, many peptide-based drugs are currently commercially available for the treatment of numerous ailments, such as hepatitis C, myeloma, skin infections, and diabetes. Initial barriers are being increasingly overcome with the development of cost-effective, more stable peptides. Herein, we review the available strategies for their synthesis, bioinformatics tools for the rational design of antimicrobial peptides with enhanced therapeutic indices, hurdles and shortcomings limiting the large-scale production of AMPs, as well as the challenges that the pharmaceutical industry faces on their use as therapeutic agents.

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References

  • Adhikari MD, Mukherjee S, Saikia J, Das G, Ramesh A (2014) Magnetic nanoparticles for selective capture and purification of an antimicrobial peptide secreted by food-grade lactic acid bacteria. J Mater Chem B Mater Biol Med 2(10):1432–1438

    CAS  Google Scholar 

  • Agopian A, Castano S (2014) Structure and orientation study of Ebola fusion peptide inserted in lipid membrane models. Biochim Biophys Acta 1838(1, Part B):117–126

    CAS  PubMed  Google Scholar 

  • Ahmad A, Ahmad E, Rabbani G, Haque S, Arshad M, Hasan Khan R (2012) Identification and design of antimicrobial peptides for therapeutic applications. Curr Protein Pept Sci 13(3):211–223

    CAS  PubMed  Google Scholar 

  • Altschul SF, Madden TL, Schäffer AA, Zhang J, Zhang Z, Miller W, Lipman DJ (1997) Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res 25(17):3389–3402

    PubMed Central  CAS  PubMed  Google Scholar 

  • Alves TP, Simões ACDC, Soares RMA, Moreno DSA, Portela MB, Castro GFBA (2014) Salivary lactoferrin in HIV-infected children: correlation with Candida albicans carriage, oral manifestations, HIV infection and its antifungal activity. Arch Oral Biol 59(8):775–782

    CAS  PubMed  Google Scholar 

  • Amado FML, Ferreira RP, Vitorino R (2013) One decade of salivary proteomics: current approaches and outstanding challenges. Clin Biochem 46(6):506–517

    CAS  PubMed  Google Scholar 

  • Anderson BF, Baker HM, Norris GE, Rice DW, Baker EN (1989) Structure of human lactoferrin: crystallographic structure analysis and refinement at 2·8 Å resolution. J Mol Biol 209(4):711–734

    CAS  PubMed  Google Scholar 

  • Avitabile C, Capparelli R, Rigano M, Fulgione A, Barone A, Pedone C, Romanelli A (2013) Antimicrobial peptides from plants: stabilization of the γ core of a tomato defensin by intramolecular disulfide bond. J Pept Sci

  • Badiani K (2012) Peptides as drugs. Manufacturing 4(2)

  • Baltzer SA, Brown MH (2011) Antimicrobial peptides—promising alternatives to conventional antibiotics. J Mol Microbiol Biotechnol 20(4):228–235

    CAS  PubMed  Google Scholar 

  • Barbiroli A, Bonomi F, Capretti G, Iametti S, Manzoni M, Piergiovanni L, Rollini M (2012) Antimicrobial activity of lysozyme and lactoferrin incorporated in cellulose-based food packaging. Food Control 26(2):387–392

    CAS  Google Scholar 

  • Bastos M, Silva T, Teixeira V, Nazmi K, Bolscher JG, Funari SS, Uhríková D (2011) Lactoferrin-derived antimicrobial peptide induces a micellar cubic phase in a model membrane system. Biophys J 101(3):L20–L22

    PubMed Central  CAS  PubMed  Google Scholar 

  • Bellamy W, Takase M, Wakabayashi H, Kawase K, Tomita M (1992) Antibacterial spectrum of lactoferricin B, a potent bactericidal peptide derived from the N‐terminal region of bovine lactoferrin. J Appl Bacteriol 73(6):472–479

    CAS  PubMed  Google Scholar 

  • Benachour H, Zaiou M, Samara A, Herbeth B, Pfister M, Lambert D, Siest G, Visvikis-Siest S (2009) Association of human cathelicidin (hCAP-18/LL-37) gene expression with cardiovascular disease risk factors. Nutr Metab Cardiovasc Dis 19(10):720–728

    CAS  PubMed  Google Scholar 

  • Bennick A (1982) Salivary proline-rich proteins. Mol Cell Biochem 45(2):83–99

    CAS  PubMed  Google Scholar 

  • Bevins CL, Salzman NH (2011) Paneth cells, antimicrobial peptides and maintenance of intestinal homeostasis. Nat Rev Microbiol 9(5):356–368

    CAS  PubMed  Google Scholar 

  • Bhardwaj R, Lightson N, Ukita Y, Takamura Y (2014) Development of oligopeptide-based novel biosensor by solid-phase peptide synthesis on microchip. Sensors Actuators B Chem 192:818–825

    CAS  Google Scholar 

  • Bi L, Yang L, Narsimhan G, Bhunia AK, Yao Y (2011) Designing carbohydrate nanoparticles for prolonged efficacy of antimicrobial peptide. J Control Release 150(2):150–156

    CAS  PubMed  Google Scholar 

  • Biyani M, Nishigaki K, Biyani M (2014) Biomolecular display technology: a new tool for drug discovery. In: Verma AS, Singh A (eds) Animal biotechnology. Academic, San Diego, pp 369–384

    Google Scholar 

  • Bodapati KC, Soudy R, Etayash H, Stiles M, Kaur K (2013) Design, synthesis and evaluation of antimicrobial activity of N-terminal modified Leucocin A analogues. Bioorg Med Chem 21(13):3715–3722

    CAS  PubMed  Google Scholar 

  • Bommarius B, Jenssen H, Elliott M, Kindrachuk J, Pasupuleti M, Gieren H, Jaeger KE, Hancock REW, Kalman D (2010) Cost-effective expression and purification of antimicrobial and host defense peptides in Escherichia coli. Peptides 31(11):1957–1965

    PubMed Central  CAS  PubMed  Google Scholar 

  • Bowdish D, Davidson D, Hancock R (2006) Immunomodulatory properties of defensins and cathelicidins. Antimicrobial Peptides and Human Disease. Springer, pp 27-66

  • Bray BL (2003) Large-scale manufacture of peptide therapeutics by chemical synthesis. Nat Rev Drug Discov 2(7):587–593

    CAS  PubMed  Google Scholar 

  • Breitling R, Klingner S, Callewaert N, Pietrucha R, Geyer A, Ehrlich G, Hartung R, Müller A, Contreras R, Beverley SM (2002) Non-pathogenic trypanosomatid protozoa as a platform for protein research and production. Protein Expr Purif 25(2):209–218

    CAS  PubMed  Google Scholar 

  • Brogden K, Heidari M, Sacco R, Palmquist D, Guthmiller J, Johnson G, Jia H, Tack B, McCray P (2003) Defensin‐induced adaptive immunity in mice and its potential in preventing periodontal disease.Oral. Microbiol Immunol 18(2):95–99

    CAS  Google Scholar 

  • Cai K, Su T, Lin S, Zheng R (2014) Molecular mechanics force field-based general map for the solvation effect on amide I probe of peptide in different micro-environments. Spectrochim Acta A Mol Biomol Spectrosc 117:548–556

    CAS  PubMed  Google Scholar 

  • Cardoso F, Pinho J, Azevedo V, Oliveira S (2006) Identification of a new Schistosoma mansoni membrane-bound protein through bioinformatic analysis. Genet Mol Res 5(4):609–618

    CAS  PubMed  Google Scholar 

  • Carrillo W, García-Ruiz A, Recio I, Moreno-Arribas MV (2014) Antibacterial activity of hen egg white lysozyme modified by heat and enzymatic treatments against oenological lactic acid bacteria and acetic acid bacteria. J Food Prot 77(10):1732–1739

    CAS  PubMed  Google Scholar 

  • Carter V, Underhill A, Baber I, Sylla L, Baby M, Larget-Thiery I, Zettor A, Bourgouin C, Langel Ü, Faye I (2013) Killer bee molecules: antimicrobial peptides as effector molecules to target sporogonic stages of Plasmodium. PLoS Pathog 9(11):e1003790

    PubMed Central  PubMed  Google Scholar 

  • Chang KY, Yang J-R (2013) Analysis and prediction of highly effective antiviral peptides based on random forests. PLoS One 8(8):e70166

    PubMed Central  CAS  PubMed  Google Scholar 

  • Cheng J, Randall AZ, Sweredoski MJ, Baldi P (2005) SCRATCH: a protein structure and structural feature prediction server. Nucleic Acids Res 33(2):W72–W76

    PubMed Central  CAS  PubMed  Google Scholar 

  • Chertov O, Michiel DF, Xu L, Wang JM, Tani K, Murphy WJ, Longo DL, Taub DD, Oppenheim JJ (1996) Identification of defensin-1, defensin-2, and CAP37/azurocidin as T-cell chemoattractant proteins released from interleukin-8-stimulated neutrophils. J Biol Chem 271(6):2935–2940

    CAS  PubMed  Google Scholar 

  • Choi H, Lee DG (2012a) Antimicrobial peptide pleurocidin synergizes with antibiotics through hydroxyl radical formation and membrane damage, and exerts antibiofilm activity. Biochim Biophys Acta 1820(12):1831–1838

    CAS  PubMed  Google Scholar 

  • Choi H, Lee DG (2012b) Synergistic effect of antimicrobial peptide arenicin-1 in combination with antibiotics against pathogenic bacteria. Res Microbiol 163(6–7):479–486

    CAS  PubMed  Google Scholar 

  • Chung SM, Wei J (2001) Clinical pharmacology and biopharmaceutics review—teriparatide. FDA - Center for Drug Evaluation and Research

  • Combet C, Jambon M, Deleage G, Geourjon C (2002) Geno3D: automatic comparative molecular modelling of protein. Bioinformatics 18(1):213–214

    CAS  PubMed  Google Scholar 

  • Conti S, Radicioni G, Ciociola T, Longhi R, Polonelli L, Gatti R, Cabras T, Messana I, Castagnola M, Vitali A (2013) Structural and functional studies on a proline-rich peptide isolated from swine saliva endowed with antifungal activity towards Cryptococcus neoformans. Biochim Biophys Acta 1828(3):1066–1074

    CAS  PubMed  Google Scholar 

  • Corrales-Garcia L, Ortiz E, Castañeda-Delgado J, Rivas-Santiago B, Corzo G (2013) Bacterial expression and antibiotic activities of recombinant variants of human β-defensins on pathogenic bacteria and M. tuberculosis. Protein Expr Purif 89(1):33–43

    CAS  PubMed  Google Scholar 

  • Costa F, Carvalho IF, Montelaro RC, Gomes P, Martins MCL (2011) Covalent immobilization of antimicrobial peptides (AMPs) onto biomaterial surfaces. Acta Biomater 7(4):1431–1440

    CAS  PubMed  Google Scholar 

  • da Silva Malheiros P, Sant’Anna V, Micheletto YMS, da Silveira NP, Brandelli A (2011) Nanovesicle encapsulation of antimicrobial peptide P34: physicochemical characterization and mode of action on Listeria monocytogenes. J Nanoparticle Res 13(8):3545–3552

    Google Scholar 

  • Dale BA, Fredericks LP (2005) Antimicrobial peptides in the oral environment: expression and function in health and disease. Curr Issues Mol Biol 7(2):119–133

    PubMed Central  CAS  PubMed  Google Scholar 

  • Davidopoulou S, Diza E, Menexes G, Kalfas S (2012) Salivary concentration of the antimicrobial peptide LL-37 in children. Arch Oral Biol 57(7):865–869

    CAS  PubMed  Google Scholar 

  • de Jong A, van Heel AJ, Kok J, Kuipers OP (2010) BAGEL2: mining for bacteriocins in genomic data. Nucleic Acids Res 38(suppl 2):W647–W651

    PubMed Central  PubMed  Google Scholar 

  • de Mello MB, da da Silva Malheiros P, Brandelli A, da Silveira NP, Jantzen MM, da Motta AS (2013) Characterization and antilisterial effect of phosphatidylcholine nanovesicles containing the antimicrobial peptide pediocin. Probiotics Antimicrob Protein 5(1):43–50

    CAS  Google Scholar 

  • de Visser PC, van Hooft PAV, de Vries A-M, de Jong A, van der Marel GA, Overkleeft HS, Noort D (2005) Biological evaluation of Tyr6 and Ser7 modified drosocin analogues. ACS Med Chem Lett 15(11):2902–2905

    Google Scholar 

  • Dean R, O’Brien L, Thwaite J, Fox M, Atkins H, Ulaeto D (2010) A carpet-based mechanism for direct antimicrobial peptide activity against vaccinia virus membranes. Peptides 31(11):1966–1972

    CAS  PubMed  Google Scholar 

  • Deléage G, Combet C, Blanchet C, Geourjon C (2001) ANTHEPROT: an integrated protein sequence analysis software with client/server capabilities. Comput Biol Med 31(4):259–267

    PubMed  Google Scholar 

  • Denny P, Hagen FK, Hardt M, Liao L, Yan W, Arellanno M, Bassilian S, Bedi GS, Boontheung P, Cociorva D, Delahunty CM, Denny T, Dunsmore J, Faull KK, Gilligan J, Gonzalez-Begne M, Halgand F, Hall SC, Han X, Henson B, Hewel J, Hu S, Jeffrey S, Jiang J, Loo JA, Ogorzalek Loo RR, Malamud D, Melvin JE, Miroshnychenko O, Navazesh M, Niles R, Park SK, Prakobphol A, Ramachandran P, Richert M, Robinson S, Sondej M, Souda P, Sullivan MA, Takashima J, Than S, Wang J, Whitelegge JP, Witkowska HE, Wolinsky L, Xie Y, Xu T, Yu W, Ytterberg J, Wong DT, Yates JR 3rd, Fisher SJ (2008) The proteomes of human parotid and submandibular/sublingual gland salivas collected as the ductal secretions. J Proteome Res 7(5):1994–2006

    PubMed Central  CAS  PubMed  Google Scholar 

  • Dhople V, Krukemeyer A, Ramamoorthy A (2006) The human beta-defensin-3, an antibacterial peptide with multiple biological functions. Biochim Biophys Acta 1758(9):1499–1512

    CAS  PubMed  Google Scholar 

  • Di Luca M, Maccari G, Nifosi R (2014) Treatment of microbial biofilms in the post-antibiotic era: prophylactic and therapeutic use of antimicrobial peptides and their design by bioinformatics tools. Pathog Dis 70(3):257–270

    PubMed  Google Scholar 

  • Diamond G, Beckloff N, Ryan LK (2008) Host defense peptides in the oral cavity and the lung: similarities and differences. J Dent Res 87(10):915–927

    PubMed Central  CAS  PubMed  Google Scholar 

  • Dings RPM, Haseman JR, Leslie DB, Luong M, Dunn DL, Mayo KH (2013) Bacterial membrane disrupting dodecapeptide SC4 improves survival of mice challenged with Pseudomonas aeruginosa. Biochim Biophys Acta 1830(6):3454–3457

    CAS  PubMed  Google Scholar 

  • Drucker DJ, Dritselis A, Kirkpatrick P (2010) Liraglutide. Nat Rev Drug Discov 9(4):267–268

    CAS  PubMed  Google Scholar 

  • Durek T, Becker CFW (2005) Protein semi-synthesis: new proteins for functional and structural studies. Biomol Eng 22(5–6):153–172

    CAS  PubMed  Google Scholar 

  • Dürr UHN, Sudheendra US, Ramamoorthy A (2006) LL-37, the only human member of the cathelicidin family of antimicrobial peptides. Biochim Biophys Acta 1758(9):1408–1425

    PubMed  Google Scholar 

  • Elsawy MA, Martin L, Tikhonova IG, Walker B (2013) Solid phase synthesis of Smac/DIABLO-derived peptides using a ‘Safety-Catch’ resin: identification of potent XIAP BIR3 antagonists. Bioorg Med Chem 21(17):5004–5011

    CAS  PubMed  Google Scholar 

  • Eriksen TH, Skovsen E, Fojan P (2013) Release of antimicrobial peptides from electrospun nanofibres as a drug delivery system. J Biomed Nanotechnol 9(3):492–498

    CAS  PubMed  Google Scholar 

  • Fábián T, Gótai L, Beck A, Fejérdy P (2009) The role of molecular chaperones (HSPAs/HSP70s) in oral health and oral inflammatory diseases: a review. Eur J Inflamm 7:53–61

    Google Scholar 

  • Fábián TK, Hermann P, Beck A, Fejérdy P, Fábián G (2012) Salivary defense proteins: their network and role in innate and acquired oral immunity. Int J Mol Sci 13(4):4295–4320

    PubMed Central  PubMed  Google Scholar 

  • Falla TJ, Zhang L (2010) Efficacy of hexapeptide-7 on menopausal skin. J Drugs Dermatol 9(1):49–54

    PubMed  Google Scholar 

  • Fernandez DI, Le Brun AP, Whitwell TC, Sani M-A, James M, Separovic F (2012) The antimicrobial peptide aurein 1.2 disrupts model membranes via the carpet mechanism. Phys Chem Chem Phys 14(45):15739–15751

    CAS  PubMed  Google Scholar 

  • Fidelis K, Kryshtafovych A (2014) Protein Structure Prediction Center. http://predictioncenter.org/. Accessed 21 Feb 2014

  • Fjell CD, Hancock REW, Cherkasov A (2007) AMPer: a database and an automated discovery tool for antimicrobial peptides. Bioinformatics 23(9):1148–1155

    CAS  PubMed  Google Scholar 

  • Franceschini A, Szklarczyk D, Frankild S, Kuhn M, Simonovic M, Roth A, Lin J, Minguez P, Bork P, von Mering C, Jensen LJ (2013) STRING v9.1: protein-protein interaction networks, with increased coverage and integration. Nucleic Acids Res 41:D808–D815

    PubMed Central  CAS  PubMed  Google Scholar 

  • Furman BL (2012) The development of Byetta (exenatide) from the venom of the Gila monster as an anti-diabetic agent. Toxicon 59(4):464–471

    CAS  PubMed  Google Scholar 

  • Ganz T (2003) Defensins: antimicrobial peptides of innate immunity. Nat Rev Immunol 3(9):710–720

    CAS  PubMed  Google Scholar 

  • Gao J, Thelen JJ, Dunker AK, Xu D (2010) Musite, a tool for global prediction of general and kinase-specific phosphorylation sites. Mol Cell Proteomics 9(12):2586–2600

    PubMed Central  CAS  PubMed  Google Scholar 

  • Gao G, Lange D, Hilpert K, Kindrachuk J, Zou Y, Cheng JTJ, Kazemzadeh-Narbat M, Yu K, Wang R, Straus SK, Brooks DE, Chew BH, Hancock REW, Kizhakkedathu JN (2011) The biocompatibility and biofilm resistance of implant coatings based on hydrophilic polymer brushes conjugated with antimicrobial peptides. Biomaterials 32(16):3899–3909

    CAS  PubMed  Google Scholar 

  • Gasteiger E, Hoogland C, Gattiker A, Wilkins MR, Appel RD, Bairoch A (2005) Protein identification and analysis tools on the ExPASy server. The proteomics protocols handbook. Springer, pp 571-607

  • Gauri SS, Mandal SM, Pati BR, Dey S (2011) Purification and structural characterization of a novel antibacterial peptide from Bellamya bengalensis: activity against ampicillin and chloramphenicol resistant Staphylococcus epidermidis. Peptides 32(4):691–696

    CAS  PubMed  Google Scholar 

  • Gazit E, Miller IR, Biggin PC, Sansom MS, Shai Y (1996) Structure and orientation of the mammalian antibacterial peptide cecropin P1 within phospholipid membranes. J Mol Biol 258(5):860–870

    CAS  PubMed  Google Scholar 

  • Goldschmidt L, Cooper DR, Derewenda ZS, Eisenberg D (2007) Toward rational protein crystallization: a Web server for the design of crystallizable protein variants. Protein Sci 16(8):1569–1576

    PubMed Central  CAS  PubMed  Google Scholar 

  • Goodwin D, Simerska P, Toth I (2012) Peptides as therapeutics with enhanced bioactivity. Curr Med Chem 19(26):4451–4461

    CAS  PubMed  Google Scholar 

  • Goren L, Pappo D, Goldberg I, Kashman Y (2009) Acyclic and cyclic thioenamino peptides: solution- and solid-phase synthesis. Tetrahedron Lett 50(9):1048–1050

    CAS  Google Scholar 

  • Gorr S-U (2009) Antimicrobial peptides of the oral cavity. Periodontol 2000 51(1):152–180

    PubMed  Google Scholar 

  • Gorr S-U (2011) Antimicrobial peptides in periodontal innate defense. Front Oral Biol 15:84–98

    PubMed Central  PubMed  Google Scholar 

  • Graul AI, Lupone B, Cruces E, Stringer M (2013) 2012 in review—part I: the year’s new drugs & biologics. Drugs Today (Barc) 49(1):33–68

    CAS  Google Scholar 

  • Guaní-Guerra E, Santos-Mendoza T, Lugo-Reyes SO, Terán LM (2010) Antimicrobial peptides: general overview and clinical implications in human health and disease. Clin Immunol 135(1):1–11

    PubMed  Google Scholar 

  • Gueguen Y, Garnier J, Robert L, Lefranc M-P, Mougenot I, de Lorgeril J, Janech M, Gross PS, Warr GW, Cuthbertson B, Barracco MA, Bulet P, Aumelas A, Yang Y, Bo D, Xiang J, Tassanakajon A, Piquemal D, Bachère E (2006) PenBase, the shrimp antimicrobial peptide penaeidin database: sequence-based classification and recommended nomenclature. Dev Comp Immunol 30(3):283–288

    CAS  PubMed  Google Scholar 

  • Guilhelmelli F, Vilela N, Albuquerque P, Derengowski LD, Silva-Pereira I, Kyaw CM (2013) Antibiotic development challenges: the various mechanisms of action of antimicrobial peptides and of bacterial resistance. Front Microbiol 9(4):353

    Google Scholar 

  • Gusman H, Grogan J, Kagan HM, Troxler RF, Oppenheim FG (2001) Salivary histatin 5 is a potent competitive inhibitor of the cysteine proteinase clostripain. FEBS Lett 489(1):97–100

    CAS  PubMed  Google Scholar 

  • Guzmán F, Barberis S, Illanes A (2007) Peptide synthesis: chemical or enzymatic. Electron J Biotechnol 10(2):279–314

    Google Scholar 

  • Habib-Valdhorn S (2013) Credit Suisse: Copaxone sales to plunge 90%.Globes Online

  • Hammami R, Fliss I (2010) Current trends in antimicrobial agent research: chemo- and bioinformatics approaches. Drug Discov Today 15(13–14):540–546

    CAS  PubMed  Google Scholar 

  • Hammami R, Fliss I (2011) Use of SciDBMaker as tool for the design of specialized biological databases. Visual analytics and interactive technologies: data, text, and web mining applications:251

  • Hammami R, Ben Hamida J, Vergoten G, Fliss I (2009) PhytAMP: a database dedicated to antimicrobial plant peptides. Nucleic Acids Res 37:D963–D968

    PubMed Central  CAS  PubMed  Google Scholar 

  • Hammami R, Zouhir A, Le Lay C, Ben Hamida J, Fliss I (2010) BACTIBASE second release: a database and tool platform for bacteriocin characterization. BMC Microbiol 27(10):22

    Google Scholar 

  • Hancock RE, Chapple DS (1999) Peptide antibiotics. Antimicrob Agents Ch 43(6):1317–1323

    CAS  Google Scholar 

  • Hanušová K, Vápenka L, Dobiáš J, Mišková L (2013) Development of antimicrobial packaging materials with immobilized glucose oxidase and lysozyme. Cent Eur J Chem 11(7):1066–1078

    Google Scholar 

  • Harris M, Mora-Montes HM, Gow NA, Coote PJ (2009) Loss of mannosylphosphate from Candida albicans cell wall proteins results in enhanced resistance to the inhibitory effect of a cationic antimicrobial peptide via reduced peptide binding to the cell surface. Microbiology 155(4):1058–1070

    CAS  PubMed  Google Scholar 

  • Hassan M, Kjos M, Nes IF, Diep DB, Lotfipour F (2012) Natural antimicrobial peptides from bacteria: characteristics and potential applications to fight against antibiotic resistance. J Appl Microbiol 113(4):723–736

    CAS  PubMed  Google Scholar 

  • Hata TR, Gallo RL (2008) Antimicrobial peptides, skin infections and atopic dermatitis. In: Seminars in cutaneous medicine and surgery. Vol 27. NIH Public Access, p 144

  • Heazlewood JL, Durek P, Hummel J, Selbig J, Weckwerth W, Walther D, Schulze WX (2008) PhosPhAt: a database of phosphorylation sites in Arabidopsis thaliana and a plant-specific phosphorylation site predictor. Nucleic Acids Res 36(suppl 1):D1015–D1021

    PubMed Central  CAS  PubMed  Google Scholar 

  • Heimpel H (2004) Congenital dyserythropoietic anemias: epidemiology, clinical significance, and progress in understanding their pathogenesis. Ann Hematol 83(10):613–621

    PubMed  Google Scholar 

  • Heinlein C, Varón Silva D, Tröster A, Schmidt J, Gross A, Unverzagt C (2011) Fragment condensation of C‐terminal pseudoproline peptides without racemization on the solid phase. Angew Chem Int Ed Engl 50(28):6406–6410

    CAS  PubMed  Google Scholar 

  • Helmerhorst EJ, Van’t Hof W, Veerman EC, Simoons-Smit I, Nieuw Amerongen AV (1997) Synthetic histatin analogues with broad-spectrum antimicrobial activity. Biochem J 326(Pt 1):39–45

    PubMed Central  CAS  PubMed  Google Scholar 

  • Helmerhorst EJ, Traboulsi G, Salih E, Oppenheim FG (2010) Mass spectrometric identification of key proteolytic cleavage sites in statherin affecting mineral homeostasis and bacterial binding domains. J Proteome Res 9(10):5413–5421

    PubMed Central  CAS  PubMed  Google Scholar 

  • Heo S-M, Ruhl S, Scannapieco FA (2013) Implications of salivary protein binding to commensal and pathogenic bacteria. J Oral Biosci 55(4):169–174

    PubMed Central  CAS  PubMed  Google Scholar 

  • Héquet A, Humblot V, Berjeaud J-M, Pradier C-M (2011) Optimized grafting of antimicrobial peptides on stainless steel surface and biofilm resistance tests. Colloids Surf B: Biointerfaces 84(2):301–309

    PubMed  Google Scholar 

  • Herbert S, Bera A, Nerz C, Kraus D, Peschel A, Goerke C, Meehl M, Cheung A, Gotz F (2007) Molecular basis of resistance to muramidase and cationic antimicrobial peptide activity of lysozyme in staphylococci. PLoS Pathog 3(7):e102

    PubMed Central  PubMed  Google Scholar 

  • Hirsch JG (1956) Phagocytin—a bactericidal substance from polymorphonuclear leucocytes. J Exp Med 103(5):589–611

    PubMed Central  CAS  PubMed  Google Scholar 

  • Hojo K, Maeda M, Kawasaki K (2004) Solid-phase peptide synthesis in water. Part 3: a water-soluble N-protecting group, 2-[phenyl (methyl) sulfonio] ethoxycarbonyl tetrafluoroborate, and its application to solid phase peptide synthesis in water. Tetrahedron 60(8):1875–1886

    CAS  Google Scholar 

  • Hojo K, Ichikawa H, Onishi M, Fukumori Y, Kawasaki K (2011) Peptide synthesis ‘in water’ by a solution-phase method using water-dispersible nanoparticle Boc-amino acid. J Pept Sci 17(7):487–492

    CAS  PubMed  Google Scholar 

  • Hoq MI, Ibrahim HR (2011) Potent antimicrobial action of triclosan–lysozyme complex against skin pathogens mediated through drug-targeted delivery mechanism. Eur J Pharm Sci 42(1–2):130–137

    CAS  PubMed  Google Scholar 

  • Horn DW, Ao G, Maugey M, Zakri C, Poulin P, Davis VA (2013) Dispersion state and fiber toughness: antibacterial lysozyme-single walled carbon nanotubes. Adv Funct Mater 23(48):6082–6090

    CAS  Google Scholar 

  • Howl J (2005) Peptide synthesis and applications. Press, Humana

    Google Scholar 

  • Hsu D, Kakade SM, Zhang T (2012) A spectral algorithm for learning hidden Markov models. J Comp Syst Sci 78(5):1460–1480

    Google Scholar 

  • Hunter HN, Jing W, Schibli DJ, Trinh T, Park IY, Kim SC, Vogel HJ (2005) The interactions of antimicrobial peptides derived from lysozyme with model membrane systems. Biochim Biophys Acta 1668(2):175–189

    CAS  PubMed  Google Scholar 

  • Huo L, Zhang K, Ling J, Peng Z, Huang X, Liu H, Gu L (2011) Antimicrobial and DNA-binding activities of the peptide fragments of human lactoferrin and histatin 5 against Streptococcus mutans. Arch Oral Biol 56(9):869–876

    CAS  PubMed  Google Scholar 

  • Ibrahim HR, Thomas U, Pellegrini A (2001) A helix-loop-helix peptide at the upper lip of the active site cleft of lysozyme confers potent antimicrobial activity with membrane permeabilization action. J Biol Chem 276(47):43767–43774

    CAS  PubMed  Google Scholar 

  • Imamura Y, Wang PL (2014) Salivary histatin 3 inhibits heat shock cognate protein 70-mediated inflammatory cytokine production through toll-like receptors in human gingival fibroblasts. J Inflamm (Lond) 11(1):4

    Google Scholar 

  • Jarczak J, Kościuczuk EM, Lisowski P, Strzałkowska N, Jóźwik A, Horbańczuk J, Krzyżewski J, Zwierzchowski L, Bagnicka E (2013) Defensins: natural component of human innate immunity. Hum Immunol 74(9):1069–1079

    CAS  PubMed  Google Scholar 

  • Jenssen H, Hamill P, Hancock REW (2006) Peptide antimicrobial agents. Clin Microbiol Rev 19(3):491–511

    PubMed Central  CAS  PubMed  Google Scholar 

  • Jiang Z, Vasil AI, Gera L, Vasil ML, Hodges RS (2011) Rational design of α-helical antimicrobial peptides to target gram-negative pathogens, Acinetobacter baumannii and Pseudomonas aeruginosa: utilization of charge, ‘specificity determinants’, total hydrophobicity, hydrophobe type and location as design parameters to improve the therapeutic ratio. Chem Biol Drug Des 77(4):225–240

    PubMed Central  PubMed  Google Scholar 

  • Jin-Jiang H, Jin-Chun L, Min L, Qing-Shan H, Guo-Dong L (2012) The design and construction of K11: a novel α-helical antimicrobial peptide. Int J Microbiol 2012:764834

    PubMed Central  PubMed  Google Scholar 

  • Joseph S, Karnik S, Nilawe P, Jayaraman VK, Idicula-Thomas S (2012) ClassAMP: a prediction tool for classification of antimicrobial peptides. IEEE/ACM Trans Comput Biol Bioinforma 9(5):1535–1538

    Google Scholar 

  • Käll L, Krogh A, Sonnhammer ELL (2007) Advantages of combined transmembrane topology and signal peptide prediction—the Phobius web server. Nucleic Acids Res 35(2):W429–W432

    PubMed Central  PubMed  Google Scholar 

  • Kaspar AA, Reichert JM (2013) Future directions for peptide therapeutics development. Drug Discov Today 18(17–18):807–817

    CAS  PubMed  Google Scholar 

  • Kavanagh K, Dowd S (2004) Histatins: antimicrobial peptides with therapeutic potential. J Pharm Pharmacol 56(3):285–289

    CAS  PubMed  Google Scholar 

  • Kneller DG, Cohen FE, Langridge R (1990) Improvements in protein secondary structure prediction by an enhanced neural network. J Mol Biol 214(1):171–182

    CAS  PubMed  Google Scholar 

  • Koch U, Hamacher M, Nussbaumer P (2014) Cheminformatics at the interface of medicinal chemistry and proteomics. Biochim Biophys Acta 1844(1, Part A):156–161

    CAS  PubMed  Google Scholar 

  • Kochańska B, Kedzia A, Kamysz W, Maćkiewicz Z, Kupryszewski G (1999) The effect of statherin and its shortened analogues on anaerobic bacteria isolated from the oral cavity. Acta Microbiol Pol 49(3–4):243–251

    Google Scholar 

  • Kokriakov VN, Koval’chuk LV, Aleshina GM, Shamova OV (2006) Cationic antimicrobial peptides as molecular immunity factors: multi-functionality. Zh Mikrobiol Epidemiol Immunobiol 2:98–105

    PubMed  Google Scholar 

  • Kountouras J, Deretzi G, Gavalas E, Zavos C, Polyzos SA, Kazakos E, Giartza-Taxidou E, Vardaka E, Kountouras C, Katsinelos P, Boziki M, Giouleme O (2014) A proposed role of human defensins in Helicobacter pylori-related neurodegenerative disorders. Med Hypotheses 82(3):368–373

    CAS  PubMed  Google Scholar 

  • Krug A, Luker GD, Barchet W, Leib DA, Akira S, Colonna M (2004) Herpes simplex virus type 1 activates murine natural interferon-producing cells through toll-like receptor 9. Blood 103(4):1433–1437

    CAS  PubMed  Google Scholar 

  • Kück P, Struck TH (2014) BaCoCa—a heuristic software tool for the parallel assessment of sequence biases in hundreds of gene and taxon partitions. Mol Phylogenet Evol 70:94–98

    PubMed  Google Scholar 

  • Lamkin MS, Oppenheim FG (1993) Structural features of salivary function. Crit Rev Oral Biol Med 4(3):251–259

    CAS  PubMed  Google Scholar 

  • Lata S, Sharma B, Raghava G (2007) Analysis and prediction of antibacterial peptides. BMC Bioinforma 8(1):263

    Google Scholar 

  • Leadbetter MR, Adams SM, Bazzini B, Fatheree PR, Karr DE, Krause KM, Lam B, Linsell MS, Nodwell MB, Pace JL (2004) Hydrophobic vancomycin derivatives with improved ADME properties: discovery of telavancin (TD-6424). J Antibiot (Tokyo) 57(5):326–336

    CAS  Google Scholar 

  • Lee S, Jilani SM, Nikolova GV, Carpizo D, Iruela-Arispe ML (2005) Processing of VEGF-A by matrix metalloproteinases regulates bioavailability and vascular patterning in tumors. J Cell Biol 169(4):681–691

    PubMed Central  CAS  PubMed  Google Scholar 

  • Leggio A, Di Gioia ML, Perri F, Liguori A (2007) N-Nosyl-α-amino acids in solution phase peptide synthesis. Tetrahedron 63(34):8164–8173

    CAS  Google Scholar 

  • Lehmann A (2008) Ecallantide (DX-88), a plasma kallikrein inhibitor for the treatment of hereditary angioedema and the prevention of blood loss in on-pump cardiothoracic surgery. Expert Opin Biol Ther 8(8):1187–1199

    CAS  PubMed  Google Scholar 

  • Lehrer RI (2013) Evolution of antimicrobial peptides: a view from the cystine chapel antimicrobial peptides and innate immunity. Springer, pp 1-27

  • Li Y (2011) Recombinant production of antimicrobial peptides in Escherichia coli: a review. Protein Expr Purif 80(2):260–267

    CAS  PubMed  Google Scholar 

  • Li Y, Chen Z (2008) RAPD: a database of recombinantly-produced antimicrobial peptides. FEMS Microbiol Lett 289(2):126–129

    CAS  PubMed  Google Scholar 

  • Li T, Bratt P, Jonsson AP, Ryberg M, Johansson I, Griffiths WJ, Bergman T, Strömberg N (2000) Possible release of an ArgGlyArgProGln pentapeptide with innate immunity properties from acidic proline-rich proteins by proteolytic activity in commensal Streptococcus and Actinomyces species. Infect Immun 68(9):5425–5429

    PubMed Central  CAS  PubMed  Google Scholar 

  • Li Y, Kadam S, Abee T, Slaghek TM, Timmermans JW, Cohen Stuart MA, Norde W, Kleijn MJ (2012) Antimicrobial lysozyme-containing starch microgel to target and inhibit amylase-producing microorganisms. Food Hydrocoll 28(1):28–35

    CAS  Google Scholar 

  • Li W, Tailhades J, O’Brien-Simpson NM, Separovic F, Otvos Jr L, Hossain MA, Wade JD (2014) Proline-rich antimicrobial peptides: potential therapeutics against antibiotic-resistant bacteria. Amino Acids:1-8

  • Lichtenstein A, Ganz T, Selsted ME, Lehrer RI (1986) In vitro tumor cell cytolysis mediated by peptide defensins of human and rabbit granulocytes. Blood 68(6):1407–1410

    CAS  PubMed  Google Scholar 

  • Lico C, Santi L, Twyman R, Pezzotti M, Avesani L (2012) The use of plants for the production of therapeutic human peptides. Plant Cell Rep 31(3):439–451

    CAS  PubMed  Google Scholar 

  • Lopez-Abarrategui C, Figueroa-Espi V, Reyes-Acosta O, Reguera E, Otero-Gonzalez AJ (2013) Magnetic nanoparticles: new players in antimicrobial peptide therapeutics. Curr Protein Pept Sci 14(7):595–606

    CAS  PubMed  Google Scholar 

  • Ludtke SJ, He K, Heller WT, Harroun TA, Yang L, Huang HW (1996) Membrane pores induced by magainin. Biochemistry 35(43):13723–13728

    CAS  PubMed  Google Scholar 

  • Lupron Worldwide Sales (2011a) http://www.evaluategroup.com/Universal/View.aspx?type=Entity&entityType=Product&id=21572&lType=modData&componentID=1002.

  • Ma T, Liu Y, Dai Q, Yao Y, He P-a (in press) A graphical representation of protein based on a novel iterated function system. Physica A: Statistical Mechanics and its Applications(0)

  • Mackay BJ, Denepitiya L, Iacono V, Krost S, Pollock J (1984) Growth-inhibitory and bactericidal effects of human parotid salivary histidine-rich polypeptides on Streptococcus mutans. Infect Immun 44(3):695–701

    PubMed Central  CAS  PubMed  Google Scholar 

  • Mader JS, Hoskin DW (2006) Cationic antimicrobial peptides as novel cytotoxic agents for cancer treatment. Expert Opin Investig Drugs 15(8):933–946

    CAS  PubMed  Google Scholar 

  • Mahindra A, Sharma KK, Jain R (2012) Rapid microwave-assisted solution-phase peptide synthesis.Tetrahedron. Lett 53(51):6931–6935

    CAS  Google Scholar 

  • Martemyanov KA, Shirokov VA, Kurnasov OV, Gudkov AT, Spirin AS (2001) Cell-free production of biologically active polypeptides: application to the synthesis of antibacterial peptide cecropin. Protein Expr Purif 21(3):456–461

    CAS  PubMed  Google Scholar 

  • Martins C, Buczynski AK, Maia LC, Siqueira WL, Castro GFBA (2013) Salivary proteins as a biomarker for dental caries—a systematic review. J Dent 41(1):2–8

    CAS  PubMed  Google Scholar 

  • McAnulty JF, Foley JD, Reid TW, Heath TD, Waller KR, Murphy CJ (2004) Suppression of cold ischemic injury in stored kidneys by the antimicrobial peptide bactenecin. Cryobiology 49(3):230–240

    CAS  PubMed  Google Scholar 

  • McKenzie HA, White Jr FH (1991) Lysozyme and α-lactalbumin: structure, function, and interrelationships. In: C.B. Anfinsen FMRJTE, David SE (eds) Advances in protein chemistry. vol Volume 41. Academic Press, pp 173-315

  • Mcphee JB, Hancock RE (2005) Function and therapeutic potential of host defence peptides. J Pept Sci 11(11):677–687

    CAS  PubMed  Google Scholar 

  • Melino S, Gallo M, Trotta E, Mondello F, Paci M, Petruzzelli R (2006) Metal-binding and nuclease activity of an antimicrobial peptide analogue of the salivary histatin 5. Biochemistry 45(51):15373–15383

    CAS  PubMed  Google Scholar 

  • Melino S, Santone C, Di Nardo P, Sarkar B (2014) Histatins: salivary peptides with copper(II)- and zinc(II)-binding motifs: perspectives for biomedical applications. FEBS J 281(3):657–672

    CAS  PubMed  Google Scholar 

  • Memarpoor-Yazdi M, Asoodeh A, Chamani J (2012) A novel antioxidant and antimicrobial peptide from hen egg white lysozyme hydrolysates. J Funct Foods 4(1):278–286

    CAS  Google Scholar 

  • Mengíbar M, Ganan M, Miralles B, Carrascosa AV, Martínez-Rodriguez AJ, Peter MG, Heras A (2011) Antibacterial activity of products of depolymerization of chitosans with lysozyme and chitosanase against Campylobacter jejuni. Carbohydr Polym 84(2):844–848

    Google Scholar 

  • Merrifield RB (1963) Solid phase peptide synthesis. I. The synthesis of a tetrapeptide. J Am Chem Soc 85(14):2149–2154

    CAS  Google Scholar 

  • Mohe NU, Chavre PS, Deshmukh BP, Muralidharan C, Lobo LJ, Pawar DS, Saksena DL (2012) Novel process for the synthesis of 37-mer peptide pramlintide. Google Patents

  • Mollica A, Pinnen F, Azzurra S, Costante R (2013) The evolution of peptide synthesis: from early days to small molecular machines. Curr Bioact Compd 9(3):184–202

    CAS  Google Scholar 

  • Murakami J, Terao Y, Morisaki I, Hamada S, Kawabata S (2012) Group A streptococcus adheres to pharyngeal epithelial cells with salivary proline-rich proteins via GrpE chaperone protein. J Biol Chem 287(26):22266–22275

    PubMed Central  CAS  PubMed  Google Scholar 

  • Murdock C, Cleveland J, Matthews K, Chikindas M (2007) The synergistic effect of nisin and lactoferrin on the inhibition of Listeria monocytogenes and Escherichia coli O157: H7. Lett Appl Microbiol 44(3):255–261

    CAS  PubMed  Google Scholar 

  • Mureev S, Kovtun O, Nguyen UTT, Alexandrov K (2009) Species-independent translational leaders facilitate cell-free expression. Nat Biotechnol 27(8):747–752

    CAS  PubMed  Google Scholar 

  • Namjoshi S, Caccetta R, Benson HAE (2008) Skin peptides: biological activity and therapeutic opportunities. J Pharm Sci 97(7):2524–2542

    CAS  PubMed  Google Scholar 

  • Nekhotiaeva N, Elmquist A, Rajarao GK, Hällbrink M, Langel U, Good L (2004) Cell entry and antimicrobial properties of eukaryotic cell-penetrating peptides. FASEB J 18(2):394–396

    CAS  PubMed  Google Scholar 

  • Neumann H, Wang K, Davis L, Garcia-Alai M, Chin JW (2010) Encoding multiple unnatural amino acids via evolution of a quadruplet-decoding ribosome. Nature 464(7287):441–444

    CAS  PubMed  Google Scholar 

  • Nguyen LT, Haney EF, Vogel HJ (2011) The expanding scope of antimicrobial peptide structures and their modes of action. Trends Biotechnol 29(9):464–472

    CAS  PubMed  Google Scholar 

  • Nicolas P, El Amri C (2009) The dermaseptin superfamily: a gene-based combinatorial library of antimicrobial peptides. Biochim Biophys Acta 1788(8):1537–1550

    CAS  PubMed  Google Scholar 

  • Ommori R, Ouji N, Mizuno F, Kita E, Ikada Y, Asada H (2013) Selective induction of antimicrobial peptides from keratinocytes by staphylococcal bacteria. Microb Pathog 56:35–39

    CAS  PubMed  Google Scholar 

  • Oppenheim F, Xu T, McMillian F, Levitz S, Diamond R, Offner G, Troxler R (1988) Histatins, a novel family of histidine-rich proteins in human parotid secretion. Isolation, characterization, primary structure, and fungistatic effects on Candida albicans. J Biol Chem 263(16):7472–7477

    CAS  PubMed  Google Scholar 

  • Oppenheim J, Biragyn A, Kwak L, Yang D (2003) Roles of antimicrobial peptides such as defensins in innate and adaptive immunity. Ann Rheum Dis 62(suppl 2):ii17–ii21

    PubMed Central  CAS  PubMed  Google Scholar 

  • Overton IM, Barton GJ (2011) Computational approaches to selecting and optimising targets for structural biology. Methods 55(1):3–11

    PubMed Central  CAS  PubMed  Google Scholar 

  • Palacios-Chaves L, Conde-Alvarez R, Gil-Ramirez Y, Zuniga-Ripa A, Grillo M, Iriarte M, Moriyon I, Gutsmann T (2012) Study on the role of lipid composition of Brucella membrane in the resistance to cationic peptides. Int J Med Microbiol 302:79

    Google Scholar 

  • Parra A, Rivas F, Lopez PE, Garcia-Granados A, Martinez A, Albericio F, Marquez N, Muñoz E (2009) Solution- and solid-phase synthesis and anti-HIV activity of maslinic acid derivatives containing amino acids and peptides. Bioorg Med Chem 17(3):1139–1145

    CAS  PubMed  Google Scholar 

  • Parra A, Martin-Fonseca S, Rivas F, Reyes-Zurita FJ, Medina-O’Donnell M, Martinez A, Garcia-Granados A, Lupiañez JA, Albericio F (2014) Semi-synthesis of acylated triterpenes from olive-oil industry wastes for the development of anticancer and anti-HIV agents. Eur J Med Chem 74:278–301

    CAS  PubMed  Google Scholar 

  • Peschel A, Sahl HG (2006) The co-evolution of host cationic antimicrobial peptides and microbial resistance. Nat Rev Microbiol 4(7):529–536

    CAS  PubMed  Google Scholar 

  • Peters BM, Shirtliff ME, Jabra-Rizk MA (2010) Antimicrobial peptides: primeval molecules or future drugs? PLoS Pathog 6(10):e1001067

    PubMed Central  PubMed  Google Scholar 

  • Petersen TN, Brunak S, von Heijne G, Nielsen H (2011) SignalP 4.0: discriminating signal peptides from transmembrane regions. Nat Methods 8(10):785–786

    CAS  PubMed  Google Scholar 

  • Phoenix DA, Dennison SR, Harris F (2013) Antimicrobial peptides: their history, evolution, and functional promiscuity antimicrobial peptides. Wiley-VCH Verlag GmbH & Co. KGaA, pp 1-37

  • Piotto SP, Sessa L, Concilio S, Iannelli P (2012) YADAMP: yet another database of antimicrobial peptides. Int J Antimicrob Agents 39(4):346–351

    CAS  PubMed  Google Scholar 

  • Pollock JJ, Denepitiya L, MacKay B, Iacono V (1984) Fungistatic and fungicidal activity of human parotid salivary histidine-rich polypeptides on Candida albicans. Infect Immun 44(3):702–707

    PubMed Central  CAS  PubMed  Google Scholar 

  • Powers J-PS, Hancock RE (2003) The relationship between peptide structure and antibacterial activity. Peptides 24(11):1681–1691

    CAS  PubMed  Google Scholar 

  • Puri S, Edgerton M (2014) How does it kill?: understanding the candidacidal mechanism of salivary histatin 5. Eukaryot Cell 13(8):958–964

    PubMed Central  CAS  PubMed  Google Scholar 

  • Pushpanathan M, Gunasekaran P, Rajendhran J (2013) Antimicrobial peptides: versatile biological properties. Int J Pept 2013:675391

    PubMed Central  PubMed  Google Scholar 

  • Qureshi A, Thakur N, Kumar M (2013) HIPdb: a database of experimentally validated HIV inhibiting peptides. PLoS One 8(1):e5490

    Google Scholar 

  • Radhakrishnan K, Halász Á, Vlachos D, Edwards JS (2010) Quantitative understanding of cell signaling: the importance of membrane organization. Curr Opin Biotechnol 21(5):677–682

    PubMed Central  CAS  PubMed  Google Scholar 

  • Raman S, Vernon R, Thompson J, Tyka M, Sadreyev R, Pei J, Kim D, Kellogg E, DiMaio F, Lange O, Kinch L, Sheffler W, Kim BH, Das R, Grishin NV, Baker D (2013) Structure prediction for CASP8 with all-atom refinement using Rosetta. Proteins 77(Suppl 9):89–99

    Google Scholar 

  • Rana M, Chatterjee S, Kochhar S, Pereira B (2006) Antimicrobial peptides: a new dawn for regulating fertility and reproductive tract infections. J Endocrinol Reprod 10(2):88–95

    Google Scholar 

  • Rapaport D, Shai Y (1991) Interaction of fluorescently labeled pardaxin and its analogues with lipid bilayers. J Biol Chem 266(35):23769–23775

    CAS  PubMed  Google Scholar 

  • Rearden A (1994) A new LIM protein containing an autoepitope homologous to "senescent cell antigen". Biochem Biophys Res Commun 201(3):1124–1131

    CAS  PubMed  Google Scholar 

  • Reboldi A, Coisne C, Baumjohann D, Benvenuto F, Bottinelli D, Lira S, Uccelli A, Lanzavecchia A, Engelhardt B, Sallusto F (2009) CC chemokine receptor 6–regulated entry of TH-17 cells into the CNS through the choroid plexus is required for the initiation of EAE. Nat Immunol 10(5):514–523

    CAS  PubMed  Google Scholar 

  • Reddy KVR, Yedery RD, Aranha C (2004) Antimicrobial peptides: premises and promises. Int J Antimicrob Agents 24(6):536–547

    CAS  PubMed  Google Scholar 

  • Reichert J (2010) Development trends for peptide therapeutics. In: Foundation PT (ed).

  • Rice P, Longden I, Bleasby A (2000) EMBOSS: The European molecular biology open software suite. Trends Genet 16(6):276–277

    CAS  PubMed  Google Scholar 

  • Rico-Mata R, De Leon-Rodriguez LM, Avila EE (2013) Effect of antimicrobial peptides derived from human cathelicidin LL-37 on Entamoeba histolytica trophozoites. Exp Parasitol 133(3):300–306

    CAS  PubMed  Google Scholar 

  • Romano-Keeler J, Wynn JL, Maron JL (2014) Great expectorations: the potential of salivary ‘omic’ approaches in neonatal intensive care. J Perinatol 34(3):169–173

    PubMed Central  CAS  PubMed  Google Scholar 

  • Roy SK (2000) Clinical pharmacology and biopharmaceutics review—desirudin. FDA - Center for Drug Evaluation and Research

  • Rozek A, Friedrich CL, Hancock RE (2000) Structure of the bovine antimicrobial peptide indolicidin bound to dodecylphosphocholine and sodium dodecyl sulfate micelles. Biochemistry 39(51):15765–15774

    CAS  PubMed  Google Scholar 

  • Russell AL, Kennedy AM, Spuches AM, Gibson WS, Venugopal D, Klapper D, Srouji AH, Bhonsle JB, Hicks RP (2011) Determining the effect of the incorporation of unnatural amino acids into antimicrobial peptides on the interactions with zwitterionic and anionic membrane model systems. Chem Phys Lipids 164(8):740–758

    CAS  PubMed  Google Scholar 

  • Rydberg HA, Carlsson N, Nordén B (2012) Membrane interaction and secondary structure of de novo designed arginine-and tryptophan peptides with dual function. Biochem Biophys Res Commun 427(2):261–265

    CAS  PubMed  Google Scholar 

  • Schmidtchen A, Pasupuleti M, Malmsten M (2014) Effect of hydrophobic modifications in antimicrobial peptides. Adv Colloid Interf Sci 205:265–274

    CAS  Google Scholar 

  • Schonwetter BS, Stolzenberg ED, Zasloff MA (1995) Epithelial antibiotics induced at sites of inflammation. Science 267(5204):1645–1648

    CAS  PubMed  Google Scholar 

  • Schwede T, Kopp J, Guex N, Peitsch MC (2003) SWISS-MODEL: an automated protein homology-modeling server. Nucleic Acids Res 31(13):3381–3385

    PubMed Central  CAS  PubMed  Google Scholar 

  • Seebah S, Suresh A, Zhuo SW, Choong YH, Chua H, Chuon D, Beuerman R, Verma C (2007) Defensins knowledgebase: a manually curated database and information source focused on the defensins family of antimicrobial peptides. Nucleic Acids Res 35:D265–D268

    PubMed Central  CAS  PubMed  Google Scholar 

  • Shai Y, Oren Z (2001) From “carpet” mechanism to de-novo designed diastereomeric cell-selective antimicrobial peptides. Peptides 22(10):1629–1641

    CAS  PubMed  Google Scholar 

  • Sharma H, Nagaraj R (2012) Antimicrobial activity of human β-defensin 4 analogs: insights into the role of disulfide linkages in modulating activity. Peptides 38(2):255–265

    CAS  PubMed  Google Scholar 

  • Shaw JE, Alattia J-R, Verity JE, Privé GG, Yip CM (2006) Mechanisms of antimicrobial peptide action: studies of indolicidin assembly at model membrane interfaces by in situ atomic force microscopy. J Struct Biol 154(1):42–58

    CAS  PubMed  Google Scholar 

  • Shpaer EG, Robinson M, Yee D, Candlin JD, Mines R, Hunkapiller T (1996) Sensitivity and selectivity in protein similarity searches: a comparison of Smith–Waterman in hardware to BLAST and FASTA. Genomics 38(2):179–191

    CAS  PubMed  Google Scholar 

  • Sinha M, Kaushik S, Kaur P, Sharma S, Singh TP (2013) Antimicrobial lactoferrin peptides: the hidden players in the protective function of a multifunctional protein. Int J Pept 2013:12

    Google Scholar 

  • Siqueiros-Cendón T, Arévalo-Gallegos S, Iglesias-Figueroa BF, García-Montoya IA, Salazar-Martínez J, Rascón-Cruz Q (2014) Immunomodulatory effects of lactoferrin. Acta Pharmacol Sin 35(5):557–566

    PubMed  Google Scholar 

  • Slater T (2014) Recent advances in modeling languages for pathway maps and computable biological networks. Drug Discov Today 19(2):193–198

    PubMed  Google Scholar 

  • Stallmann HP, Faber C, Bronckers ALJJ, de Blieck-Hogervorst JMA, Brouwer CPJM, Amerongen AVN, Wuisman PIJM (2005) Histatin and lactoferrin derived peptides: antimicrobial properties and effects on mammalian cells. Peptides 26(12):2355–2359

    CAS  PubMed  Google Scholar 

  • Sugimoto J, Kanehira T, Mizugai H, Chiba I, Morita M (2006) Relationship between salivary histatin 5 levels and Candida CFU counts in healthy elderly. Gerodontology 23(3):164–169

    PubMed  Google Scholar 

  • Szilagyi A, Zhang Y (2014) Template-based structure modeling of protein–protein interactions. Curr Opin Struct Biol 24:10–23

    CAS  PubMed  Google Scholar 

  • Taboureau O (2010) Methods for building quantitative structure-activity relationship (QSAR) descriptors and predictive models for computer-aided design of antimicrobial peptides. Methods Mol Biol 618:77–86

    CAS  PubMed  Google Scholar 

  • Thayer A (2011) Making peptides at large scale. Chem Eng News 89(22):81–85

    Google Scholar 

  • Ting C-H, Huang H-N, Huang T-C, Wu C-J, Chen J-Y (2014) The mechanisms by which pardaxin, a natural cationic antimicrobial peptide, targets the endoplasmic reticulum and induces c-FOS. Biomaterials 35(11):3627–3640

    CAS  PubMed  Google Scholar 

  • Torrent M, Di Tommaso P, Pulido D, Nogues MV, Notredame C, Boix E (2012) Andreu D (2012) AMPA: an automated web server for prediction of protein antimicrobial regions. Bioinformatics 28(1):130–131

    CAS  PubMed  Google Scholar 

  • Torres NI, Noll KS, Xu S, Li J, Huang Q, Sinko PJ, Wachsman MB, Chikindas ML (2013) Safety, formulation and in vitro antiviral activity of the antimicrobial peptide subtilosin against herpes simplex virus type 1. Probiotics Antimicrob Protein 5(1):26–35

    CAS  Google Scholar 

  • Tossi A, Sandri L, Giangaspero A (2002) New consensus hydrophobicity scale extended to non-proteinogenic amino acids. Peptides 27:416

    Google Scholar 

  • Upton M, Cotter P, Tagg J (2012) Antimicrobial peptides as therapeutic agents. Int J Microbiol 2012:326503

  • Urban P, Valle-Delgado JJ, Moles E, Marques J, Diez C (2012) Fernandez-Busquets X (2012) Nanotools for the delivery of antimicrobial peptides. Curr Drug Targets 13(9):1158–1172

    CAS  PubMed  Google Scholar 

  • Van Wetering S, Mannesse-Lazeroms SPG, Van Sterkenburg MAJA, Daha MR, Dijkman JH, Hiemstra PS (1997) Effect of defensins on interleukin-8 synthesis in airway epithelial cells. Am J Physiol Lung Cell Mol Physiol 272(5 16-5):L888–L896

    Google Scholar 

  • Vandamme D, Landuyt B, Luyten W, Schoofs L (2012) A comprehensive summary of LL-37, the factotum human cathelicidin peptide. Cell Immunol 280(1):22–35

    CAS  PubMed  Google Scholar 

  • Vigneaud V, Ressler C, Swan CJM, Roberts CW, Katsoyannis PG, Gordon S (1953) The synthesis of an octapeptide amide with the hormonal activity of oxytocin. J Am Chem Soc 75(19):4879–4880

    Google Scholar 

  • Vlieghe P, Lisowski V, Martinez J, Khrestchatisky M (2010) Synthetic therapeutic peptides: science and market. Drug Discov Today 15(1–2):40–56

    CAS  PubMed  Google Scholar 

  • Vollmer W, Bertsche U (2008) Murein (peptidoglycan) structure, architecture and biosynthesis in Escherichia coli. Biochim Biophys Acta 1778(9):1714–1734

    CAS  PubMed  Google Scholar 

  • Waghu FH, Gopi L, Barai RS, Ramteke P, Nizami B, Idicula-Thomas S (2014) CAMP: collection of sequences and structures of antimicrobial peptides. Nucleic Acids Res 42(D1):D1154–D1158

    PubMed Central  CAS  PubMed  Google Scholar 

  • Wang G (2008) Structures of human host defense cathelicidin LL-37 and its smallest antimicrobial peptide KR-12 in lipid micelles. J Biol Chem 283(47):32637–32643

    CAS  PubMed  Google Scholar 

  • Wang CKL, Kaas Q, Chiche L, Craik DJ (2008) CyBase: a database of cyclic protein sequences and structures, with applications in protein discovery and engineering. Nucleic Acids Res 36(1):D206–D210

    PubMed Central  CAS  PubMed  Google Scholar 

  • Wang G, Li X, Wang Z (2009) APD2: the updated antimicrobial peptide database and its application in peptide design. Nucleic Acids Res 37:D933–D937

    PubMed Central  CAS  PubMed  Google Scholar 

  • Wang H, Xu K, Liu L, Tan JPK, Chen Y, Li Y, Fan W, Wei Z, Sheng J, Yang Y-Y, Li L (2010) The efficacy of self-assembled cationic antimicrobial peptide nanoparticles against Cryptococcus neoformans for the treatment of meningitis. Biomaterials 31(10):2874–2881

    CAS  PubMed  Google Scholar 

  • Wang K, Schmied WH, Chin JW (2012) Reprogramming the genetic code: from triplet to quadruplet codes. Angew Chem Int Ed Engl 51(10):2288–2297

    CAS  PubMed  Google Scholar 

  • Wang G, Mishra B, Epand RF, Epand RM (2014) High-quality 3D structures shine light on antibacterial, anti-biofilm and antiviral activities of human cathelicidin LL-37 and its fragments. Biochim Biophys Acta 1838(9):2160–2172

    CAS  PubMed  Google Scholar 

  • Ward BP, Ottaway NL, Perez-Tilve D, Ma D, Gelfanov VM, Tschöp MH, DiMarchi RD (2013) Peptide lipidation stabilizes structure to enhance biological function. Mol Metab 2(4):468–479

    PubMed Central  CAS  PubMed  Google Scholar 

  • Were LM, Bruce B, Davidson PM, Weiss J (2004) Encapsulation of nisin and lysozyme in liposomes enhances efficacy against Listeria monocytogenes. J Food Prot 67(5):922–927

    CAS  PubMed  Google Scholar 

  • Whitmore L, Wallace BA (2004) The Peptaibol database: a database for sequences and structures of naturally occurring peptaibols. Nucleic Acids Res 32:D593–D594

    PubMed Central  CAS  PubMed  Google Scholar 

  • Wilson SS, Wiens ME, Smith JG (2013) Antiviral mechanisms of human defensins. J Mol Biol 425(24):4965–4980

    CAS  PubMed  Google Scholar 

  • Wimley WC (2010) Describing the mechanism of antimicrobial peptide action with the interfacial activity model. ACS Chem Biol 5(10):905–917

    PubMed Central  CAS  PubMed  Google Scholar 

  • Wimley W, Hristova K (2011) Antimicrobial peptides: successes, challenges and unanswered questions. J Membr Biol 239(1–2):27–34

    PubMed Central  CAS  PubMed  Google Scholar 

  • Wöhr T, Wahl F, Nefzi A, Rohwedder B, Sato T, Sun X, Mutter M (1996) Pseudo-prolines as a solubilizing, structure-disrupting protection technique in peptide synthesis. J Am Chem Soc 118(39):9218–9227

    Google Scholar 

  • Workman P, Collins I (2014) Modern cancer drug discovery: integrating targets, technologies, and treatments for personalized medicine. In: Neidle S (ed) Cancer drug design and discovery, 2nd edn. Academic, San Diego, pp 3–53

    Google Scholar 

  • Xi D, Teng D, Wang X, Mao R, Yang Y, Xiang W, Wang J (2013) Design, expression and characterization of the hybrid antimicrobial peptide LHP7, connected by a flexible linker, against Staphylococcus and Streptococcus. Process Biochem 48(3):453–461

    CAS  Google Scholar 

  • Xiong Y-Q, Bayer AS, Yeaman MR (2002) Inhibition of intracellular macromolecular synthesis in Staphylococcus aureus by thrombin-induced platelet microbicidal proteins. J Infect Dis 185(3):348–356

    CAS  PubMed  Google Scholar 

  • Xu F, Meng K, Wang Y-R, Luo H-Y, Yang P-L, Wu N-F, Fan Y-L, Yao B (2008) Eukaryotic expression and antimicrobial spectrum determination of the peptide tachyplesin II. Protein Expr Purif 58(2):175–183

    CAS  PubMed  Google Scholar 

  • Yeaman MR, Yount NY (2003) Mechanisms of antimicrobial peptide action and resistance. Pharmacol Rev 55(1):27–55

    CAS  PubMed  Google Scholar 

  • Yeung AT, Gellatly SL, Hancock RE (2011) Multifunctional cationic host defence peptides and their clinical applications. Cell Mol Life Sci 68(13):2161–2176

    CAS  PubMed  Google Scholar 

  • Yoshimura K, Toibana A, Nakahama K (1988) Human lysozyme: sequencing of a cDNA, and expression and secretion by Saccharomyces cerevisiae. Biochem Biophys Res Commun 150(2):794–801

    CAS  PubMed  Google Scholar 

  • Zarember KA, Cruz AR, Huang C-Y, Gallin JI (2009) Antifungal activities of natural and synthetic iron chelators alone and in combination with azole and polyene antibiotics against Aspergillus fumigatus. Antimicrob Agents Ch 53(6):2654–2656

    CAS  Google Scholar 

  • Zeya HI, Spitznag JK (1966) Cationic proteins of polymorphonuclear leukocyte lysosomes. 2. Composition properties and mechanism of antibacterial action. J Bacteriol 91(2):755

    PubMed Central  CAS  PubMed  Google Scholar 

  • Zhang X, Oglęcka K, Sandgren S, Belting M, Esbjörner EK, Nordén B, Gräslund A (2010) Dual functions of the human antimicrobial peptide LL-37—target membrane perturbation and host cell cargo delivery. Biochim Biophys Acta 1798(12):2201–2208

    CAS  PubMed  Google Scholar 

  • Zhu S, Gao B (2013) Evolutionary origin of β-defensins. Dev Comp Immunol 39(1–2):79–84

    CAS  PubMed  Google Scholar 

  • Ziserman L, Lee H-Y, Raghavan SR, Mor A, Danino D (2011) Unraveling the mechanism of nanotube formation by chiral self-assembly of amphiphiles. J Am Chem Soc 133(8):2511–2517

    CAS  PubMed  Google Scholar 

  • Zoladex Worldwide Sales (2011b) http://www.evaluategroup.com/Universal/View.aspx?type=Entity&entityType=Product&id=21572&lType=modData&componentID=1002#&&_ViewArgs=%7b%22_EntityType%22%3a0%2c%22_Parameters%22%3a%7b%22_ContextData%22%3a%22zoladex%22%7d%2c%22_Type%22%3a5%7d.

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Acknowledgments

This work was supported by the Fundação para a Ciência e a Tecnologia (FCT, Portugal), European Union, QREN, FEDER, and COMPETE for funding the QOPNA research unit (project PEst-C/QUI/UI0062/2013), research project (PTDC/EXPL/BBB-BEP/0317/2012; QREN (FCOMP-01-0124-FEDER-027554), and to CENTRO-07-ST24-FEDER-002034 (co-financiated by QREN, Mais Centro-Programa Operacional Regional do Centro e União Europeia/ Fundo Europeu de Desenvolvimento Regional).

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    Authors and Affiliations

    1. Mass Spectrometry Centre, QOPNA, Department of Chemistry, University of Aveiro, 3810-193, Aveiro, Portugal

      João Pinto da Costa, Marta Cova, Rita Ferreira & Rui Vitorino

    2. Institute for Research in Biomedicine – iBiMED, Health Sciences Program, University of Aveiro, 3810-193, Aveiro, Portugal

      Rui Vitorino

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    1. João Pinto da Costa
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    2. Marta Cova
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    3. Rita Ferreira
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    4. Rui Vitorino
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    Correspondence to Rui Vitorino.

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    João Pinto da Costa and Marta Cova contributed equally to this work.

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    da Costa, J.P., Cova, M., Ferreira, R. et al. Antimicrobial peptides: an alternative for innovative medicines?. Appl Microbiol Biotechnol 99, 2023–2040 (2015). https://doi.org/10.1007/s00253-015-6375-x

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