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Short peptides as biosensor transducers

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Abstract

This review deals with short peptides (up to 50 amino acids) as biomimetic active recognition elements in sensing systems. Peptide-based sensors have been developed in recent years according to different strategies. Synthetic peptides have been designed on the basis of known interactions between single or a few amino acids and targets, with attention being paid to the presence of peptide motifs known to allow intermolecular self-organization of the sensing peptides over the sensor surface. Sensitive and sophisticated sensors have been obtained in this way, but the use of designed peptides is limited by severe difficulties in their in silico design. Short peptides from random phage display have been selected in a random way from large, unfocussed, and often preexisting and commercially available phage display libraries, with no design elements. Such peptides often perform better than antibodies, but they are difficult to select when the target is a small molecule because of the need to immobilize it with considerable modifications of its structure. Artificial, miniaturized receptors have been obtained from the reduction of the known sequence of a natural receptor down to a synthesizable and yet stable one. Alternatively, binding sites have been created over a designed, stable peptide scaffold. Short peptides have also been used as active elements for the detection of their own natural receptors: pathogenic bacteria have been detected with antimicrobial and cell-penetrating peptides, but key challenges such as detection of bacteria in real samples, improved sensitivity, and improved selectivity have to be faced. Peptide substrates have been conjugated to fluorescent quantum dots to obtain disposable sensors for protease activity with high sensitivity. Ferrocene–peptide conjugates have been used for electrochemical sensing of protease activity.

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Abbreviations

ACPP:

activatable cell-penetrating peptide

AMP:

antimicrobial peptide

CPP:

cell-penetrating peptide

ELISA:

enzyme-linked immunosorbant assay

Fc:

ferrocene

FRET:

Förster resonance energy transfer

LOD:

limit of detection

MPA:

mercaptoproprionic acid

PCR:

polymerase chain reaction

QCM:

quartz crystal microbalance

QD:

quantum dot

SAM:

self-assembled monolayer

SNAP-25:

synaptosomal-associated protein 25

SPRI:

surface plasmon resonance imaging

TAT:

transactivator of transcription

TNT:

2,4,6-trinitrotoluene

References

  1. Tewari AK, Dubey R (2008) Bioorg Med Chem 16:126–143

    Article  CAS  Google Scholar 

  2. Chiari M, Cretich M, Damin F, Di Carlo G, Oldani C (2008) J Chromatogr B 866:89–103

    Article  CAS  Google Scholar 

  3. Ariga K, Hill JP, Endo H (2007) Int J Mol Sci 8:864–883

    Article  CAS  Google Scholar 

  4. Zarzo M (2007) Biol Rev 82:455–479

    Article  Google Scholar 

  5. Skerra A (2007) Curr Opin Biotechnol 18(4):295–304

    Article  CAS  Google Scholar 

  6. Chow E, Gooding JJ (2006) Electroanalysis 18(15):1437–1448

    Article  CAS  Google Scholar 

  7. Bi X, Agarwal A, Balasubramanian N, Yang KL (2008) Electrochem Commun 10:1868–1871

    Article  CAS  Google Scholar 

  8. Lin M, Cho M, Choe WS, Yoo JB, Lee Y (2010) Biosens Biolectron 26(2):940–945

    Article  CAS  Google Scholar 

  9. Xu YM, Pan HQ, Wu SH, Zhang BL (2009) Chin J Anal Chem 37(6):783–787

    Article  CAS  Google Scholar 

  10. Viguier B, Zòr K, Kasotakis E, Mitraki A, Clausen CH, Svendsen WE, Castillo-Leòn J (2011) ACS Appl Mater Interfaces 3:1594–1600

    Article  CAS  Google Scholar 

  11. Godwin HA, Berg JM (1996) J Am Chem Soc 118(27):6514–6515

    Article  CAS  Google Scholar 

  12. Villiers MB, Cortès S, Brakha C, Lavergne JP, Marquette CA, Deny P, Livache T, Marche PN (2010) Biosens Bioelectron 26(4):1554–1559

    Article  CAS  Google Scholar 

  13. De La Rica R, Pejoux C, Matsui H (2011) Adv Funct Mater 21(6):1018–1026

    Article  Google Scholar 

  14. Lu HH, Rao YK, Wu TZ, Tzeng YM (2009) Sens Actuators B Chem 137(2):741–746

    Article  Google Scholar 

  15. Mascini M, Macagnano A, Scortichini G, Del Carlo M, Diletti G, D'Amico A, Di Natale C, Compagnone D (2005) Sens Actuators B Chem 111–112(Suppl):376–384

    Article  Google Scholar 

  16. Nakamura C, Inuyama Y, Goto H, Obataya I, Kaneko N, Nakamura N, Santo N, Miyake J (2005) Anal Chem 77:7750–7757

    Article  CAS  Google Scholar 

  17. Obataya I, Nakamura C, Enomoto H, Hoshino T, Nakamura N, Miyake J (2004) J Mol Catal B 28:265–271

    Article  CAS  Google Scholar 

  18. Duchesne L, Wells G, Fernig DG, Harris SA, Lévy R (2008) Chembiochem 9(13):2127–2134

    Article  CAS  Google Scholar 

  19. Venanzi M, Pace G, Palleschi A, Stella L, Castrucci P, Scarselli M, De Crescenzi M, Formaggio F, Toniolo C, Marletta G (2006) Surf Sci 600(2):409–416

    Article  CAS  Google Scholar 

  20. Miura Y, Kimura S, Imanishi Y, Umemura J (1998) Langmuir 14(10):2761–2767

    Article  CAS  Google Scholar 

  21. Pomerantz WC, Cadwell KD, Hsu Y-J, Gellman SH, Abbott NL (2007) Chem Mater 19(18):4436–4441

    Article  CAS  Google Scholar 

  22. Lévy R (2006) Chembiochem 7(8):1141–1145

    Article  Google Scholar 

  23. Bolduc OR, Clouthier CM, Pelletier JN, Masson JF (2009) Anal Chem 81(16):6779–6788

    Article  CAS  Google Scholar 

  24. Lévy R, Thanh NT, Doty RC, Hussain I, Nichols RJ, Schiffrin DJ, Brust M, Fernig DG (2004) J Am Chem Soc 126(32):10076–10084

    Article  Google Scholar 

  25. Frisk ML, Tepp WH, Johnson EA, Beebe DJ (2009) Anal Chem 81(7):2760–2767

    Article  CAS  Google Scholar 

  26. Tseng MC, Chang YP, Chu YH (2007) Anal Biochem 371(1):1–9

    Article  CAS  Google Scholar 

  27. Aili D, Selegård R, Enander K, Liedberg B (2009) Small 5:2445–2452

    Article  CAS  Google Scholar 

  28. Enander K, Dolphin GT, Baltzer L (2004) J Am Chem Soc 126:4464–4465

    Article  CAS  Google Scholar 

  29. Smith GP, Petrenko VA (1997) Chem Rev 97:391–410

    Article  CAS  Google Scholar 

  30. Bradbury ARM (2010) Curr Protoc Neurosci 5.12.1–5.12.27

  31. Drevelle A, Graille M, Heyd B, Sorelle I, Ulryck N, Pecorari F, Desmadril M, van Tilbeurgh H, Minard P (2006) J Mol Biol 358:455–471

    Article  CAS  Google Scholar 

  32. Schweitzer BI, Dicker AP, Bertino JR (1990) FASEB J 4(8):2441–2452

    CAS  Google Scholar 

  33. Goldman ER, Pazirandeh MP, Charles PT, Balighian ED, Anderson GP (2002) Anal Chim Acta 457:13–19

    Article  CAS  Google Scholar 

  34. Benedetti F, Berti F, Brady K, Colombatti A, Pauletto A, Pucillo C, Thomas NR (2004) Chembiochem 5(1):129–131

    Article  CAS  Google Scholar 

  35. Nakamura C, Song SH, Chang SM, Sugimoto N, Miyake J (2002) Anal Chim Acta 469:183–188

    Article  CAS  Google Scholar 

  36. Riugrok VJB, Levisson M, Eppkin MHM, Smidt H, van der Oost J (2011) Biochem J 436:1–13

    Article  Google Scholar 

  37. Zoller F, Haberkorn U, Mier W (2011) Molecules 16(3):2467–2485

    Article  CAS  Google Scholar 

  38. Goldman ER, Pazirandeh MP, Mauro M, King KD, Frey JC, Anderson GP (2000) J Mol Recognit 13:382–387

    Article  CAS  Google Scholar 

  39. Paige LA, Christensen DJ, Grøn H, Norris JD, Gottlin EB, Padilla KM, Chang CY, Ballas LM, Hamilton PT, McDonnell DP, Fowlkes DM (1999) Proc Natl Acad Sci USA 96(7):3999–4004

    Article  CAS  Google Scholar 

  40. Fechner P, Pröll F, Carlquist M, Proll G (2009) Anal Bioanal Chem 393(6–7):1579–1585

    Google Scholar 

  41. Samoylov AM, Samoylova TI, Pathirana ST, Globa LP, Vodyanoy VJ (2002) J Mol Recognit 15:197–203

    Article  CAS  Google Scholar 

  42. Carnazza S, Foti C, Gioffrè G, Felici F, Guglielmino S (2007) Biosens Biolectron 23:1137–1144

    Article  Google Scholar 

  43. Zhang H, Li X, Bay I, Niu R, Jia Y, Zhang C, Zhang L, Cao Y (2009) Biotechnol Appl Biochem 53(3):185–192

    CAS  Google Scholar 

  44. Huan TN, Ha VTT, Hung LQ, Yoon MY, Han SH, Chung H (2009) Biosens Bioelectron 25:469–474

    Article  CAS  Google Scholar 

  45. Anderson GP, King KD, Gaffney KL, Johnson LH (2000) Biosens Bioelecton 14:771–778

    Article  CAS  Google Scholar 

  46. Wu J, Cropek DM, West AC, Banta S (2010) Anal Chem 82:8235–8243

    Article  CAS  Google Scholar 

  47. Zhu H, White IM, Suter JD, Fan X (2008) Biosens Bioelectron 24(3):461–466

    Article  CAS  Google Scholar 

  48. Skerra A (2007) Curr Opin Biotechnol 18:259–304

    Article  Google Scholar 

  49. Nord K, Nillson B, Nillson M, Uhlèn M, Nygren PÅ (1995) Protein Eng 8

  50. Nord K, Gunneriusson J, Ringdahl S, Ståhl M, Uhlèn M, Nygren PÅ (1997) Nat Biotechnol 15:772–777

    Article  CAS  Google Scholar 

  51. Renberg B, Shiroyama I, Engfeldt T, Nygren PÅ, Karlström AE (2005) Anal Biochem 341:334–343

    Article  CAS  Google Scholar 

  52. Renberg B, Nordin J, Merca A, Uhlèn M, Feldwish J, Nygren PÅ, Karlström AE (2007) J Proteome Res 6:171–179

    Article  CAS  Google Scholar 

  53. Gao J, Chen K, Miao Z, Ren G, Xiaoyuan C, Gambir SS, Cheng Z (2011) Biomaterials 32:2141–2148

    Article  CAS  Google Scholar 

  54. Hou Y, Gochin M (2008) Anal Chem 80:5924–5929

    Article  CAS  Google Scholar 

  55. Weiss-Wichert C, Valina-Saba M, Schalkhammer T (1997) J Biomol Screen 2:11–18

    Article  CAS  Google Scholar 

  56. Albrecht C, Fechner P, Honcharenko D, Gauglitz G (2010) Biosens Bioelectron 25:2302–2308

    Article  CAS  Google Scholar 

  57. Savoini A (2006) Italian Patent Application RM2006 A00707

  58. Chao H, Bautista DL, Litowsky J, Irvin TR, Hodges RS (1996) J Chromatogr B Biomed Sci Appl 715:307–309

    Article  Google Scholar 

  59. Frisk ML, Guangyun L, Johnson EA, Beebe DJ (2011) Biosens Bioelectron 26:1929–1935

    Article  CAS  Google Scholar 

  60. Anai T, Nakata E, Koshi Y, Ojida A, Hamachi I (2007) J Am Chem Soc 129:6232–6239

    Article  CAS  Google Scholar 

  61. Asakawa H, Mochitate K, Haruyama T (2008) Anal Chem 80:1505–1511

    Article  CAS  Google Scholar 

  62. Sankaran S, Panigrahi S, Mallik S (2011) Biosens Bioelectron 26(7):3103–3109

    Article  CAS  Google Scholar 

  63. Wu TZ, Lo YR, Chan EC (2001) Biosens Bioelectron 16(9–12):945–953

    Article  CAS  Google Scholar 

  64. Sankaran S, Panigrahi S, Mallik S (2011) Sens Actuators B Chem 155(1):8–18

    Article  Google Scholar 

  65. Kulagina NV, Lassman ME, Ligler FS, Taitt CR (2005) Anal Chem 77(19):6504–6508

    Article  CAS  Google Scholar 

  66. Kulagina NV, Shaffer KM, Anderson GP, Ligler FS, Taitt CR (2006) Anal Chim Acta 575(1):9–15

    Article  CAS  Google Scholar 

  67. Arcidiacono S, Pivarnik P, Mello CM, Senecal A (2008) Biosens Bioelectron 23(11):1721–1727

    Article  CAS  Google Scholar 

  68. Kulagina NV, Shaffer KM, Ligler FS, Taitt CR (2007) Sens Actuators B Chem 121(1):150–157

    Article  Google Scholar 

  69. Zampa MF, Araújo IM, Costa V, Nery Costa CH, Santos JR Jr, Zucolotto V, Eiras C, Leite JR (2009) Nanomedicine 5(3):352–358

    Article  CAS  Google Scholar 

  70. Mannoor MS, Zhang S, Link AJ, McAlpine MC (2010) Proc Natl Acad Sci USA 107(45):19207–19212

    Article  CAS  Google Scholar 

  71. Thorén PE, Persson D, Esbjörner EK, Goksör M, Lincoln P (2004) Nordén B 43(12):3471–3489

    Google Scholar 

  72. Fonseca SB, Pereira MP, Kelley SO (2009) Adv Drug Deliv Rev 61(11):953–964

    Article  CAS  Google Scholar 

  73. Seward GK, Wei Q, Dmochowski IJ (2008) Bioconjug Chem 19(11):2129–2135

    Article  CAS  Google Scholar 

  74. Cho Y, Ivanisevic A (2005) J Phys Chem B 109(13):6225–6232

    Article  CAS  Google Scholar 

  75. Cho Y, Ivanisevic A (2006) Langmuir 22(4):1768–1774

    Article  CAS  Google Scholar 

  76. Aguilera TA, Olson ES, Timmers MM, Jiang T, Tsien RY (2009) Integr Biol (Camb) 371–381

  77. Raha S, Paunesku T, Woloschak G (2011) Wiley Interdiscip Rev Nanomed Nanobiotechnol 3(3):269–281

    Article  CAS  Google Scholar 

  78. Olson ES, Jiang T, Aguilera TA, Nguyen QT, Ellies LG, Scadeng M, Tsien RY (2010) Proc Natl Acad Sci USA 107(9):4311–4316

    Article  CAS  Google Scholar 

  79. Bi X, Yang KL (2010) Biosens Bioelectron 26(1):107–111

    Article  CAS  Google Scholar 

  80. Matayoshi ED, Wang GT, Krafft GA, Erickson J (1990) Science 247(4945):954–958

    Article  CAS  Google Scholar 

  81. Grahn S, Ullmann D, Jakubke H (1998) Anal Biochem 265(2):225–231

    Article  CAS  Google Scholar 

  82. Schmidt JJ, Stafford RG (2003) Appl Environ Microbiol 2069(1):297–303

    Article  Google Scholar 

  83. Prasuhn DE, Feltz A, Blanco-Canosa JB, Susumu K, Stewart MH, Mei BC, Yakovlev AV, Loukov C, Mallet JM, Oheim M, Dawson PE, Medintz IL (2010) ACS Nano 4(9):5487–5497

    Article  CAS  Google Scholar 

  84. Sapsford KE, Granek J, Deschamps JR, Boeneman K, Blanco-Canosa JB, Dawson PE, Susumu K, Stewart MH, Medintz IL (2011) ACS Nano 5(4):2687–2699

    Article  CAS  Google Scholar 

  85. Sapsford KE, Farrell D, Sun S, Rasooly A, Mattoussi H, Medintz IL (2009) Sens Actuators B Chem 139(1):13–21

    Article  Google Scholar 

  86. Kilian KA, Böcking T, Gaus K, Gal M, Gooding JJ (2007) ACS Nano (4):355–361

  87. Liu G, Wang J, Wunschel DS, Lin YJ (2006) Am Chem Soc 128(38):12382–12383

    Article  CAS  Google Scholar 

  88. Adjémian J, Anne A, Cauet G, Demaille C (2010) Langmuir 26(12):10347–10356

    Article  Google Scholar 

  89. Ohtsuka K, Maekawa I, Waki M, Takenaka S (2009) Anal Biochem 385(2):293–299

    Article  CAS  Google Scholar 

  90. Mahmoud KA, Kraatz HB (2007) Chemistry 13(20):5885–5895

    Article  CAS  Google Scholar 

  91. Xiao H, Liu L, Meng F, Huang J, Li G (2008) Anal Chem 80(13):5272–5275

    Article  CAS  Google Scholar 

  92. Kerman K, Mahmoud KA, Kraatz HB (2007) Chem Commun 3829–3831

  93. Mahmoud KA, Hrapovic S, Luong JH (2008) ACS Nano 2(5):1051–1057

    Article  CAS  Google Scholar 

  94. Ghadiali JE, Cohen BE, Stevens MM (2010) ACS Nano 4(8):4915–4919

    Article  CAS  Google Scholar 

  95. Uri A, Lust M, Vaasa A, Lavogina D, Viht K, Enkvist E (2010) Biochim Biophys Acta 1804(3):541–546

    CAS  Google Scholar 

  96. Sullivan TP, van Poll ML, Dankers PY, Huck WT (2004) Angew Chem Int Ed 43(32):4190–4193

    Article  CAS  Google Scholar 

  97. Cui Y, Pattabiraman A, Lisko B, Collins SC, McAlpine MC (2010) J Am Chem Soc 132(4):1204–1205

    Article  CAS  Google Scholar 

  98. Grasso G, D'Agata R, Rizzarelli E, Spoto G, D'Andrea L, Pedone C, Picardi A, Romanelli A, Fragai M, Yeo KJ (2005) J Mass Spectrom 40(12):1565–1571

    Article  CAS  Google Scholar 

  99. Fu J, Reinhold J, Woodbury NW (2011) PLoS One 6(4):e18692

    Article  CAS  Google Scholar 

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Acknowledgements

We are grateful to the Commissariato del Governo nella Regione Friuli—Venezia Giulia (Fondo Trieste) for a grant to S.P. (Grant 597/08 “Piccoli peptidi per lo sviluppo di biosensori”). We are grateful to Chiara Carletti-Vagni for her helpful suggestions during the revision process.

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Correspondence to Federico Berti.

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Published in the topical collection Biomimetic Recognition Elements for Sensing Applications with guest editor María Cruz Moreno-Bondi.

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Pavan, S., Berti, F. Short peptides as biosensor transducers. Anal Bioanal Chem 402, 3055–3070 (2012). https://doi.org/10.1007/s00216-011-5589-8

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