Applied Microbiology and Biotechnology

, Volume 99, Issue 5, pp 2023–2040 | Cite as

Antimicrobial peptides: an alternative for innovative medicines?

  • João Pinto da Costa
  • Marta Cova
  • Rita Ferreira
  • Rui Vitorino


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.


Salivary peptide Antitumoral Synthesis Bioinformatics 



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).

Conflict of interest

The authors declare no conflict of interest.


  1. 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):1432–1438Google Scholar
  2. 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):117–126PubMedGoogle Scholar
  3. 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):211–223PubMedGoogle Scholar
  4. 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):3389–3402PubMedCentralPubMedGoogle Scholar
  5. 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):775–782PubMedGoogle Scholar
  6. Amado FML, Ferreira RP, Vitorino R (2013) One decade of salivary proteomics: current approaches and outstanding challenges. Clin Biochem 46(6):506–517PubMedGoogle Scholar
  7. 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):711–734PubMedGoogle Scholar
  8. 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 SciGoogle Scholar
  9. Badiani K (2012) Peptides as drugs. Manufacturing 4(2)Google Scholar
  10. Baltzer SA, Brown MH (2011) Antimicrobial peptides—promising alternatives to conventional antibiotics. J Mol Microbiol Biotechnol 20(4):228–235PubMedGoogle Scholar
  11. 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):387–392Google Scholar
  12. 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–L22PubMedCentralPubMedGoogle Scholar
  13. 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):472–479PubMedGoogle Scholar
  14. 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):720–728PubMedGoogle Scholar
  15. Bennick A (1982) Salivary proline-rich proteins. Mol Cell Biochem 45(2):83–99PubMedGoogle Scholar
  16. Bevins CL, Salzman NH (2011) Paneth cells, antimicrobial peptides and maintenance of intestinal homeostasis. Nat Rev Microbiol 9(5):356–368PubMedGoogle Scholar
  17. 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 192:818–825Google Scholar
  18. 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):150–156PubMedGoogle Scholar
  19. 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 369–384Google Scholar
  20. 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):3715–3722PubMedGoogle Scholar
  21. 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):1957–1965PubMedCentralPubMedGoogle Scholar
  22. Bowdish D, Davidson D, Hancock R (2006) Immunomodulatory properties of defensins and cathelicidins. Antimicrobial Peptides and Human Disease. Springer, pp 27-66Google Scholar
  23. Bray BL (2003) Large-scale manufacture of peptide therapeutics by chemical synthesis. Nat Rev Drug Discov 2(7):587–593PubMedGoogle Scholar
  24. 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):209–218PubMedGoogle Scholar
  25. 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):95–99Google Scholar
  26. 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 117:548–556PubMedGoogle Scholar
  27. 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):609–618PubMedGoogle Scholar
  28. 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):1732–1739PubMedGoogle Scholar
  29. 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):e1003790PubMedCentralPubMedGoogle Scholar
  30. Chang KY, Yang J-R (2013) Analysis and prediction of highly effective antiviral peptides based on random forests. PLoS One 8(8):e70166PubMedCentralPubMedGoogle Scholar
  31. Cheng J, Randall AZ, Sweredoski MJ, Baldi P (2005) SCRATCH: a protein structure and structural feature prediction server. Nucleic Acids Res 33(2):W72–W76PubMedCentralPubMedGoogle Scholar
  32. 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):2935–2940PubMedGoogle Scholar
  33. 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):1831–1838PubMedGoogle Scholar
  34. Choi H, Lee DG (2012b) Synergistic effect of antimicrobial peptide arenicin-1 in combination with antibiotics against pathogenic bacteria. Res Microbiol 163(6–7):479–486PubMedGoogle Scholar
  35. Chung SM, Wei J (2001) Clinical pharmacology and biopharmaceutics review—teriparatide. FDA - Center for Drug Evaluation and ResearchGoogle Scholar
  36. Combet C, Jambon M, Deleage G, Geourjon C (2002) Geno3D: automatic comparative molecular modelling of protein. Bioinformatics 18(1):213–214PubMedGoogle Scholar
  37. 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):1066–1074PubMedGoogle Scholar
  38. 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):33–43PubMedGoogle Scholar
  39. Costa F, Carvalho IF, Montelaro RC, Gomes P, Martins MCL (2011) Covalent immobilization of antimicrobial peptides (AMPs) onto biomaterial surfaces. Acta Biomater 7(4):1431–1440PubMedGoogle Scholar
  40. 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):3545–3552Google Scholar
  41. Dale BA, Fredericks LP (2005) Antimicrobial peptides in the oral environment: expression and function in health and disease. Curr Issues Mol Biol 7(2):119–133PubMedCentralPubMedGoogle Scholar
  42. Davidopoulou S, Diza E, Menexes G, Kalfas S (2012) Salivary concentration of the antimicrobial peptide LL-37 in children. Arch Oral Biol 57(7):865–869PubMedGoogle Scholar
  43. 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–W651PubMedCentralPubMedGoogle Scholar
  44. 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):43–50Google Scholar
  45. 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):2902–2905Google Scholar
  46. 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):1966–1972PubMedGoogle Scholar
  47. 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):259–267PubMedGoogle Scholar
  48. 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):1994–2006PubMedCentralPubMedGoogle Scholar
  49. Dhople V, Krukemeyer A, Ramamoorthy A (2006) The human beta-defensin-3, an antibacterial peptide with multiple biological functions. Biochim Biophys Acta 1758(9):1499–1512PubMedGoogle Scholar
  50. 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):257–270PubMedGoogle Scholar
  51. 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):915–927PubMedCentralPubMedGoogle Scholar
  52. 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):3454–3457PubMedGoogle Scholar
  53. Drucker DJ, Dritselis A, Kirkpatrick P (2010) Liraglutide. Nat Rev Drug Discov 9(4):267–268PubMedGoogle Scholar
  54. Durek T, Becker CFW (2005) Protein semi-synthesis: new proteins for functional and structural studies. Biomol Eng 22(5–6):153–172PubMedGoogle Scholar
  55. 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):1408–1425PubMedGoogle Scholar
  56. 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):5004–5011PubMedGoogle Scholar
  57. Eriksen TH, Skovsen E, Fojan P (2013) Release of antimicrobial peptides from electrospun nanofibres as a drug delivery system. J Biomed Nanotechnol 9(3):492–498PubMedGoogle Scholar
  58. 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 7:53–61Google Scholar
  59. 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):4295–4320PubMedCentralPubMedGoogle Scholar
  60. Falla TJ, Zhang L (2010) Efficacy of hexapeptide-7 on menopausal skin. J Drugs Dermatol 9(1):49–54PubMedGoogle Scholar
  61. 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):15739–15751PubMedGoogle Scholar
  62. Fidelis K, Kryshtafovych A (2014) Protein Structure Prediction Center. Accessed 21 Feb 2014
  63. Fjell CD, Hancock REW, Cherkasov A (2007) AMPer: a database and an automated discovery tool for antimicrobial peptides. Bioinformatics 23(9):1148–1155PubMedGoogle Scholar
  64. 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–D815PubMedCentralPubMedGoogle Scholar
  65. Furman BL (2012) The development of Byetta (exenatide) from the venom of the Gila monster as an anti-diabetic agent. Toxicon 59(4):464–471PubMedGoogle Scholar
  66. Ganz T (2003) Defensins: antimicrobial peptides of innate immunity. Nat Rev Immunol 3(9):710–720PubMedGoogle Scholar
  67. 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):2586–2600PubMedCentralPubMedGoogle Scholar
  68. 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):3899–3909PubMedGoogle Scholar
  69. 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 571-607Google Scholar
  70. 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):691–696PubMedGoogle Scholar
  71. 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):860–870PubMedGoogle Scholar
  72. 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):1569–1576PubMedCentralPubMedGoogle Scholar
  73. Goodwin D, Simerska P, Toth I (2012) Peptides as therapeutics with enhanced bioactivity. Curr Med Chem 19(26):4451–4461PubMedGoogle Scholar
  74. Goren L, Pappo D, Goldberg I, Kashman Y (2009) Acyclic and cyclic thioenamino peptides: solution- and solid-phase synthesis. Tetrahedron Lett 50(9):1048–1050Google Scholar
  75. Gorr S-U (2009) Antimicrobial peptides of the oral cavity. Periodontol 2000 51(1):152–180PubMedGoogle Scholar
  76. Gorr S-U (2011) Antimicrobial peptides in periodontal innate defense. Front Oral Biol 15:84–98PubMedCentralPubMedGoogle Scholar
  77. 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):33–68Google Scholar
  78. 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):1–11PubMedGoogle Scholar
  79. 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):283–288PubMedGoogle Scholar
  80. 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):353Google Scholar
  81. 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):97–100PubMedGoogle Scholar
  82. Guzmán F, Barberis S, Illanes A (2007) Peptide synthesis: chemical or enzymatic. Electron J Biotechnol 10(2):279–314Google Scholar
  83. Habib-Valdhorn S (2013) Credit Suisse: Copaxone sales to plunge 90%.Globes OnlineGoogle Scholar
  84. Hammami R, Fliss I (2010) Current trends in antimicrobial agent research: chemo- and bioinformatics approaches. Drug Discov Today 15(13–14):540–546PubMedGoogle Scholar
  85. 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:251Google Scholar
  86. Hammami R, Ben Hamida J, Vergoten G, Fliss I (2009) PhytAMP: a database dedicated to antimicrobial plant peptides. Nucleic Acids Res 37:D963–D968PubMedCentralPubMedGoogle Scholar
  87. 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):22Google Scholar
  88. Hancock RE, Chapple DS (1999) Peptide antibiotics. Antimicrob Agents Ch 43(6):1317–1323Google Scholar
  89. 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):1066–1078Google Scholar
  90. 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):1058–1070PubMedGoogle Scholar
  91. 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):723–736PubMedGoogle Scholar
  92. 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 144Google Scholar
  93. 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–D1021PubMedCentralPubMedGoogle Scholar
  94. Heimpel H (2004) Congenital dyserythropoietic anemias: epidemiology, clinical significance, and progress in understanding their pathogenesis. Ann Hematol 83(10):613–621PubMedGoogle Scholar
  95. 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):6406–6410PubMedGoogle Scholar
  96. 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):39–45PubMedCentralPubMedGoogle Scholar
  97. 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):5413–5421PubMedCentralPubMedGoogle Scholar
  98. Heo S-M, Ruhl S, Scannapieco FA (2013) Implications of salivary protein binding to commensal and pathogenic bacteria. J Oral Biosci 55(4):169–174PubMedCentralPubMedGoogle Scholar
  99. 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):301–309PubMedGoogle Scholar
  100. 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):e102PubMedCentralPubMedGoogle Scholar
  101. Hirsch JG (1956) Phagocytin—a bactericidal substance from polymorphonuclear leucocytes. J Exp Med 103(5):589–611PubMedCentralPubMedGoogle Scholar
  102. 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):1875–1886Google Scholar
  103. 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):487–492PubMedGoogle Scholar
  104. 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):130–137PubMedGoogle Scholar
  105. 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):6082–6090Google Scholar
  106. Howl J (2005) Peptide synthesis and applications. Press, HumanaGoogle Scholar
  107. Hsu D, Kakade SM, Zhang T (2012) A spectral algorithm for learning hidden Markov models. J Comp Syst Sci 78(5):1460–1480Google Scholar
  108. 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):175–189PubMedGoogle Scholar
  109. 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):869–876PubMedGoogle Scholar
  110. 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):43767–43774PubMedGoogle Scholar
  111. 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):4Google Scholar
  112. 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):1069–1079PubMedGoogle Scholar
  113. Jenssen H, Hamill P, Hancock REW (2006) Peptide antimicrobial agents. Clin Microbiol Rev 19(3):491–511PubMedCentralPubMedGoogle Scholar
  114. 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):225–240PubMedCentralPubMedGoogle Scholar
  115. 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 2012:764834PubMedCentralPubMedGoogle Scholar
  116. 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):1535–1538Google Scholar
  117. 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–W432PubMedCentralPubMedGoogle Scholar
  118. Kaspar AA, Reichert JM (2013) Future directions for peptide therapeutics development. Drug Discov Today 18(17–18):807–817PubMedGoogle Scholar
  119. Kavanagh K, Dowd S (2004) Histatins: antimicrobial peptides with therapeutic potential. J Pharm Pharmacol 56(3):285–289PubMedGoogle Scholar
  120. Kneller DG, Cohen FE, Langridge R (1990) Improvements in protein secondary structure prediction by an enhanced neural network. J Mol Biol 214(1):171–182PubMedGoogle Scholar
  121. Koch U, Hamacher M, Nussbaumer P (2014) Cheminformatics at the interface of medicinal chemistry and proteomics. Biochim Biophys Acta 1844(1, Part A):156–161PubMedGoogle Scholar
  122. 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):243–251Google Scholar
  123. Kokriakov VN, Koval’chuk LV, Aleshina GM, Shamova OV (2006) Cationic antimicrobial peptides as molecular immunity factors: multi-functionality. Zh Mikrobiol Epidemiol Immunobiol 2:98–105PubMedGoogle Scholar
  124. 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):368–373PubMedGoogle Scholar
  125. 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):1433–1437PubMedGoogle Scholar
  126. 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 70:94–98PubMedGoogle Scholar
  127. Lamkin MS, Oppenheim FG (1993) Structural features of salivary function. Crit Rev Oral Biol Med 4(3):251–259PubMedGoogle Scholar
  128. Lata S, Sharma B, Raghava G (2007) Analysis and prediction of antibacterial peptides. BMC Bioinforma 8(1):263Google Scholar
  129. 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):326–336Google Scholar
  130. 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):681–691PubMedCentralPubMedGoogle Scholar
  131. Leggio A, Di Gioia ML, Perri F, Liguori A (2007) N-Nosyl-α-amino acids in solution phase peptide synthesis. Tetrahedron 63(34):8164–8173Google Scholar
  132. 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):1187–1199PubMedGoogle Scholar
  133. Lehrer RI (2013) Evolution of antimicrobial peptides: a view from the cystine chapel antimicrobial peptides and innate immunity. Springer, pp 1-27Google Scholar
  134. Li Y (2011) Recombinant production of antimicrobial peptides in Escherichia coli: a review. Protein Expr Purif 80(2):260–267PubMedGoogle Scholar
  135. Li Y, Chen Z (2008) RAPD: a database of recombinantly-produced antimicrobial peptides. FEMS Microbiol Lett 289(2):126–129PubMedGoogle Scholar
  136. 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):5425–5429PubMedCentralPubMedGoogle Scholar
  137. 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):28–35Google Scholar
  138. 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:1-8Google Scholar
  139. 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):1407–1410PubMedGoogle Scholar
  140. 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):439–451PubMedGoogle Scholar
  141. 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):595–606PubMedGoogle Scholar
  142. Ludtke SJ, He K, Heller WT, Harroun TA, Yang L, Huang HW (1996) Membrane pores induced by magainin. Biochemistry 35(43):13723–13728PubMedGoogle Scholar
  143. 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)Google Scholar
  144. 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):695–701PubMedCentralPubMedGoogle Scholar
  145. Mader JS, Hoskin DW (2006) Cationic antimicrobial peptides as novel cytotoxic agents for cancer treatment. Expert Opin Investig Drugs 15(8):933–946PubMedGoogle Scholar
  146. Mahindra A, Sharma KK, Jain R (2012) Rapid microwave-assisted solution-phase peptide synthesis.Tetrahedron. Lett 53(51):6931–6935Google Scholar
  147. 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):456–461PubMedGoogle Scholar
  148. 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):2–8PubMedGoogle Scholar
  149. 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):230–240PubMedGoogle Scholar
  150. 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 173-315Google Scholar
  151. Mcphee JB, Hancock RE (2005) Function and therapeutic potential of host defence peptides. J Pept Sci 11(11):677–687PubMedGoogle Scholar
  152. 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):15373–15383PubMedGoogle Scholar
  153. 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):657–672PubMedGoogle Scholar
  154. 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):278–286Google Scholar
  155. 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):844–848Google Scholar
  156. Merrifield RB (1963) Solid phase peptide synthesis. I. The synthesis of a tetrapeptide. J Am Chem Soc 85(14):2149–2154Google Scholar
  157. 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 PatentsGoogle Scholar
  158. 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):184–202Google Scholar
  159. 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):22266–22275PubMedCentralPubMedGoogle Scholar
  160. 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):255–261PubMedGoogle Scholar
  161. Mureev S, Kovtun O, Nguyen UTT, Alexandrov K (2009) Species-independent translational leaders facilitate cell-free expression. Nat Biotechnol 27(8):747–752PubMedGoogle Scholar
  162. Namjoshi S, Caccetta R, Benson HAE (2008) Skin peptides: biological activity and therapeutic opportunities. J Pharm Sci 97(7):2524–2542PubMedGoogle Scholar
  163. 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):394–396PubMedGoogle Scholar
  164. 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):441–444PubMedGoogle Scholar
  165. Nguyen LT, Haney EF, Vogel HJ (2011) The expanding scope of antimicrobial peptide structures and their modes of action. Trends Biotechnol 29(9):464–472PubMedGoogle Scholar
  166. Nicolas P, El Amri C (2009) The dermaseptin superfamily: a gene-based combinatorial library of antimicrobial peptides. Biochim Biophys Acta 1788(8):1537–1550PubMedGoogle Scholar
  167. 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 56:35–39PubMedGoogle Scholar
  168. 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):7472–7477PubMedGoogle Scholar
  169. 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–ii21PubMedCentralPubMedGoogle Scholar
  170. Overton IM, Barton GJ (2011) Computational approaches to selecting and optimising targets for structural biology. Methods 55(1):3–11PubMedCentralPubMedGoogle Scholar
  171. 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 302:79Google Scholar
  172. 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):1139–1145PubMedGoogle Scholar
  173. 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 74:278–301PubMedGoogle Scholar
  174. Peschel A, Sahl HG (2006) The co-evolution of host cationic antimicrobial peptides and microbial resistance. Nat Rev Microbiol 4(7):529–536PubMedGoogle Scholar
  175. Peters BM, Shirtliff ME, Jabra-Rizk MA (2010) Antimicrobial peptides: primeval molecules or future drugs? PLoS Pathog 6(10):e1001067PubMedCentralPubMedGoogle Scholar
  176. Petersen TN, Brunak S, von Heijne G, Nielsen H (2011) SignalP 4.0: discriminating signal peptides from transmembrane regions. Nat Methods 8(10):785–786PubMedGoogle Scholar
  177. Phoenix DA, Dennison SR, Harris F (2013) Antimicrobial peptides: their history, evolution, and functional promiscuity antimicrobial peptides. Wiley-VCH Verlag GmbH & Co. KGaA, pp 1-37Google Scholar
  178. Piotto SP, Sessa L, Concilio S, Iannelli P (2012) YADAMP: yet another database of antimicrobial peptides. Int J Antimicrob Agents 39(4):346–351PubMedGoogle Scholar
  179. 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):702–707PubMedCentralPubMedGoogle Scholar
  180. Powers J-PS, Hancock RE (2003) The relationship between peptide structure and antibacterial activity. Peptides 24(11):1681–1691PubMedGoogle Scholar
  181. Puri S, Edgerton M (2014) How does it kill?: understanding the candidacidal mechanism of salivary histatin 5. Eukaryot Cell 13(8):958–964PubMedCentralPubMedGoogle Scholar
  182. Pushpanathan M, Gunasekaran P, Rajendhran J (2013) Antimicrobial peptides: versatile biological properties. Int J Pept 2013:675391PubMedCentralPubMedGoogle Scholar
  183. Qureshi A, Thakur N, Kumar M (2013) HIPdb: a database of experimentally validated HIV inhibiting peptides. PLoS One 8(1):e5490Google Scholar
  184. Radhakrishnan K, Halász Á, Vlachos D, Edwards JS (2010) Quantitative understanding of cell signaling: the importance of membrane organization. Curr Opin Biotechnol 21(5):677–682PubMedCentralPubMedGoogle Scholar
  185. 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):89–99Google Scholar
  186. 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):88–95Google Scholar
  187. Rapaport D, Shai Y (1991) Interaction of fluorescently labeled pardaxin and its analogues with lipid bilayers. J Biol Chem 266(35):23769–23775PubMedGoogle Scholar
  188. Rearden A (1994) A new LIM protein containing an autoepitope homologous to "senescent cell antigen". Biochem Biophys Res Commun 201(3):1124–1131PubMedGoogle Scholar
  189. 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):514–523PubMedGoogle Scholar
  190. Reddy KVR, Yedery RD, Aranha C (2004) Antimicrobial peptides: premises and promises. Int J Antimicrob Agents 24(6):536–547PubMedGoogle Scholar
  191. Reichert J (2010) Development trends for peptide therapeutics. In: Foundation PT (ed).Google Scholar
  192. Rice P, Longden I, Bleasby A (2000) EMBOSS: The European molecular biology open software suite. Trends Genet 16(6):276–277PubMedGoogle Scholar
  193. 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):300–306PubMedGoogle Scholar
  194. Romano-Keeler J, Wynn JL, Maron JL (2014) Great expectorations: the potential of salivary ‘omic’ approaches in neonatal intensive care. J Perinatol 34(3):169–173PubMedCentralPubMedGoogle Scholar
  195. Roy SK (2000) Clinical pharmacology and biopharmaceutics review—desirudin. FDA - Center for Drug Evaluation and ResearchGoogle Scholar
  196. 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):15765–15774PubMedGoogle Scholar
  197. 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):740–758PubMedGoogle Scholar
  198. 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):261–265PubMedGoogle Scholar
  199. Schmidtchen A, Pasupuleti M, Malmsten M (2014) Effect of hydrophobic modifications in antimicrobial peptides. Adv Colloid Interf Sci 205:265–274Google Scholar
  200. Schonwetter BS, Stolzenberg ED, Zasloff MA (1995) Epithelial antibiotics induced at sites of inflammation. Science 267(5204):1645–1648PubMedGoogle Scholar
  201. Schwede T, Kopp J, Guex N, Peitsch MC (2003) SWISS-MODEL: an automated protein homology-modeling server. Nucleic Acids Res 31(13):3381–3385PubMedCentralPubMedGoogle Scholar
  202. 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–D268PubMedCentralPubMedGoogle Scholar
  203. Shai Y, Oren Z (2001) From “carpet” mechanism to de-novo designed diastereomeric cell-selective antimicrobial peptides. Peptides 22(10):1629–1641PubMedGoogle Scholar
  204. 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):255–265PubMedGoogle Scholar
  205. 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):42–58PubMedGoogle Scholar
  206. 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):179–191PubMedGoogle Scholar
  207. 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 2013:12Google Scholar
  208. 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):557–566PubMedGoogle Scholar
  209. Slater T (2014) Recent advances in modeling languages for pathway maps and computable biological networks. Drug Discov Today 19(2):193–198PubMedGoogle Scholar
  210. 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):2355–2359PubMedGoogle Scholar
  211. 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):164–169PubMedGoogle Scholar
  212. Szilagyi A, Zhang Y (2014) Template-based structure modeling of protein–protein interactions. Curr Opin Struct Biol 24:10–23PubMedGoogle Scholar
  213. 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 618:77–86PubMedGoogle Scholar
  214. Thayer A (2011) Making peptides at large scale. Chem Eng News 89(22):81–85Google Scholar
  215. 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):3627–3640PubMedGoogle Scholar
  216. 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):130–131PubMedGoogle Scholar
  217. 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):26–35Google Scholar
  218. Tossi A, Sandri L, Giangaspero A (2002) New consensus hydrophobicity scale extended to non-proteinogenic amino acids. Peptides 27:416Google Scholar
  219. Upton M, Cotter P, Tagg J (2012) Antimicrobial peptides as therapeutic agents. Int J Microbiol 2012:326503Google Scholar
  220. 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):1158–1172PubMedGoogle Scholar
  221. 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–L896Google Scholar
  222. Vandamme D, Landuyt B, Luyten W, Schoofs L (2012) A comprehensive summary of LL-37, the factotum human cathelicidin peptide. Cell Immunol 280(1):22–35PubMedGoogle Scholar
  223. 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):4879–4880Google Scholar
  224. Vlieghe P, Lisowski V, Martinez J, Khrestchatisky M (2010) Synthetic therapeutic peptides: science and market. Drug Discov Today 15(1–2):40–56PubMedGoogle Scholar
  225. Vollmer W, Bertsche U (2008) Murein (peptidoglycan) structure, architecture and biosynthesis in Escherichia coli. Biochim Biophys Acta 1778(9):1714–1734PubMedGoogle Scholar
  226. 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–D1158PubMedCentralPubMedGoogle Scholar
  227. 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):32637–32643PubMedGoogle Scholar
  228. 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–D210PubMedCentralPubMedGoogle Scholar
  229. Wang G, Li X, Wang Z (2009) APD2: the updated antimicrobial peptide database and its application in peptide design. Nucleic Acids Res 37:D933–D937PubMedCentralPubMedGoogle Scholar
  230. 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):2874–2881PubMedGoogle Scholar
  231. Wang K, Schmied WH, Chin JW (2012) Reprogramming the genetic code: from triplet to quadruplet codes. Angew Chem Int Ed Engl 51(10):2288–2297PubMedGoogle Scholar
  232. 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):2160–2172PubMedGoogle Scholar
  233. 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):468–479PubMedCentralPubMedGoogle Scholar
  234. 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):922–927PubMedGoogle Scholar
  235. Whitmore L, Wallace BA (2004) The Peptaibol database: a database for sequences and structures of naturally occurring peptaibols. Nucleic Acids Res 32:D593–D594PubMedCentralPubMedGoogle Scholar
  236. Wilson SS, Wiens ME, Smith JG (2013) Antiviral mechanisms of human defensins. J Mol Biol 425(24):4965–4980PubMedGoogle Scholar
  237. Wimley WC (2010) Describing the mechanism of antimicrobial peptide action with the interfacial activity model. ACS Chem Biol 5(10):905–917PubMedCentralPubMedGoogle Scholar
  238. Wimley W, Hristova K (2011) Antimicrobial peptides: successes, challenges and unanswered questions. J Membr Biol 239(1–2):27–34PubMedCentralPubMedGoogle Scholar
  239. 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):9218–9227Google Scholar
  240. 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 3–53Google Scholar
  241. 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):453–461Google Scholar
  242. 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):348–356PubMedGoogle Scholar
  243. 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):175–183PubMedGoogle Scholar
  244. Yeaman MR, Yount NY (2003) Mechanisms of antimicrobial peptide action and resistance. Pharmacol Rev 55(1):27–55PubMedGoogle Scholar
  245. Yeung AT, Gellatly SL, Hancock RE (2011) Multifunctional cationic host defence peptides and their clinical applications. Cell Mol Life Sci 68(13):2161–2176PubMedGoogle Scholar
  246. 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):794–801PubMedGoogle Scholar
  247. 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):2654–2656Google Scholar
  248. Zeya HI, Spitznag JK (1966) Cationic proteins of polymorphonuclear leukocyte lysosomes. 2. Composition properties and mechanism of antibacterial action. J Bacteriol 91(2):755PubMedCentralPubMedGoogle Scholar
  249. 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):2201–2208PubMedGoogle Scholar
  250. Zhu S, Gao B (2013) Evolutionary origin of β-defensins. Dev Comp Immunol 39(1–2):79–84PubMedGoogle Scholar
  251. 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):2511–2517PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • João Pinto da Costa
    • 1
  • Marta Cova
    • 1
  • Rita Ferreira
    • 1
  • Rui Vitorino
    • 1
    • 2
  1. 1.Mass Spectrometry Centre, QOPNA, Department of ChemistryUniversity of AveiroAveiroPortugal
  2. 2.Institute for Research in Biomedicine – iBiMED, Health Sciences ProgramUniversity of AveiroAveiroPortugal

Personalised recommendations