Combinatorially Developed Peptide Receptors for Biosensors

Part of the Integrated Analytical Systems book series (ANASYS)


Various combinatorial libraries were screened for short peptides of 4–10 mer, which were used as sensor molecules for capturing target chemicals or biomolecules. Immuno-antibodies can be synthesized in the living bodies of higher animals even for low-molecular-weight nonnatural chemical compounds, such as dioxins or PCBs. Recently, some peptide ligands that can even bind to inorganic crystals have been reported. This indicates that the 20 natural amino acids have the potential to recognize almost all types of molecules and substances. The question arises whether one should design a “rational” mini library of peptides consisting of a limited number of amino acids according to the motifs in epitopes or paratopes or the binding pocket sequences in receptors, or a completely “random” combinatorial library containing all sequences. If one wants to obtain a peptide binder to target a small chemical compound, the answer is a “random” library, since the molecular interaction between the target compound and an amino acid cannot be precisely predicted beforehand. In this section, we discuss the possibility of using short combinatorial peptides as binders for biosensors to detect chemical compounds.


Surface Plasmon Resonance Quartz Crystal Microbalance Surface Plasmon Resonance Sensor Natural Amino Acid Surface Plasmon Resonance Signal 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Morita, Y.; Ohsugi, T.; Iwasa, Y.; Tamiya, E., A screening of phage displayed peptides for the recognition of fullerene (c60). J. Mol. Catal. B: Enzym. 2004, 28, 185–190CrossRefGoogle Scholar
  2. 2.
    Sano, K.; Shiba, K., A hexapeptide motif that electrostatically binds to the surface of titanium. J. Am. Chem. Soc. 2003, 125, 14234–14235CrossRefGoogle Scholar
  3. 3.
    Su, Z.; Leung, T.; Honek, J. F., Conformational selectivity of peptides for single-walled carbon nanotubes. J. Phys. Chem. B Condens. Matter. Mater. Surf. Interfaces Biophys. 2006, 110, 23623–23627Google Scholar
  4. 4.
    Wang, G.; De, J.; Schoeniger, J.; Roe, D.; Carbonell, R., A hexamer peptide ligand that binds selectively to staphylococcal enterotoxin b: Isolation from a solid phase combinatorial library. J. Pept. Res. 2004, 64, 51–64.CrossRefGoogle Scholar
  5. 5.
    Mascini, M.; Macagnano, A.; Monti, D.; Del Carlo, M.; Paolesse, R.; Chen, B.; Warner, P.; D’Amico, A.; Di Natale, C.; Compagnone, D., Piezoelectric sensors for dioxins: A biomimetic approach. Biosens. Bioelectron. 2004, 20, 1203–1210CrossRefGoogle Scholar
  6. 6.
    Boon, C. L.; Frost, D.; Chakrabartty, A., Identification of stable helical bundles from a combinatorial library of amphipathic peptides. Biopolymers 2004, 76, 244–257CrossRefGoogle Scholar
  7. 7.
    Obataya, I.; Kotaki, T.; Sakamoto, S.; Ueno, A.; Mihara, H., Design, synthesis and peroxidase-like activity of 3alpha-helix proteins covalently bound to heme. Bioorg. Med. Chem. Lett. 2000, 10, 2719–2722CrossRefGoogle Scholar
  8. 8.
    Obataya, I.; Sakamoto, S.; Ueno, A.; Mihara, H., Design and synthesis of 3alpha-helix peptides forming a cavity for a fluorescent ligand. Biopolymers 2001, 59, 65–71CrossRefGoogle Scholar
  9. 9.
    Fukumori, T.; Morita, Y.; Tamiya, E.; Yokoyama, K., Design of peptide that recognizes double-stranded DNA. Anal. Sci. 2003, 19, 181–183CrossRefGoogle Scholar
  10. 10.
    Meyer, S. C.; Gaj, T.; Ghosh, I., Highly selective cyclic peptide ligands for neutravidin and avidin identified by phage display. Chem. Biol. Drug. Des. 2006, 68, 3–10CrossRefGoogle Scholar
  11. 11.
    Qin, C.; Bu, X.; Zhong, X.; Ng, N. L.; Guo, Z., Optimization of antibacterial cyclic decapeptides. J. Comb. Chem. 2004, 6, 398–406CrossRefGoogle Scholar
  12. 12.
    Fink, A. L., Natively unfolded proteins. Curr. Opin. Struct. Biol. 2005, 15, 35–41CrossRefGoogle Scholar
  13. 13.
    Kawakami, J.; Kitano, T.; Sugimoto, N., A selection of short peptides that interact with a porphyrin as a small target by immobilized phage display. Chem. Commun. 1999, 1765–1766Google Scholar
  14. 14.
    Karlsson, R.; Stahlberg, R., Surface plasmon resonance detection and multispot sensing for direct monitoring of interactions involving low-molecular-weight analytes and for determination of low affinities. Anal. Biochem. 1995, 228, 274–280CrossRefGoogle Scholar
  15. 15.
    Nakamura, C.; Inuyama, Y.; Shirai, K.; Nakano, S.; Sugimoto, N.; Miyake, J., Analysis for peptide binding to porphyrin using surface plasmon resonance. Synthetic Met. 2001, 117, 127–129CrossRefGoogle Scholar
  16. 16.
    Nakamura, C.; Inuyama, Y.; Shirai, K.; Sugimoto, N.; Miyake, J., Detection of porphyrin using a short peptide immobilized on a surface plasmon resonance sensor chip. Biosens. Bioelectron 2001, 16, 1095–1100CrossRefGoogle Scholar
  17. 17.
    Kanazawa, K.; Gordon, J. G., The oscillation frequency of a quartz resonator in contact with liquid. Anal. Chem. Acta 1985, 175, 99–105CrossRefGoogle Scholar
  18. 18.
    Nakamura, C.; Song, S.-H.; Chang, S.-M.; Sugimoto, N.; Miyake, J., Quartz crystal microbalance sensor targeting low molecular weight compounds using oligopeptide binder and peptide-immobilized latex beads. J. Anal. Chim. Acta. 2002, 469, 183–188CrossRefGoogle Scholar
  19. 19.
    Sugimoto, N.; Nakano, S., Sandwiching interaction of peptides with a porphyrin. Chem. Lett. 1997, 939–940Google Scholar
  20. 20.
    Grandbois, M.; Beyer, M.; Rief, M.; Clausen-Schaumann, H.; Gaub, H. E., How strong is a covalent bond? Science 1999, 283, 1727CrossRefGoogle Scholar
  21. 21.
    Florin, E. L.; Moy, V. T.; Gaub, H. E., Adhesion forces between individual ligand-recepter pairs. Science 1994, 264, 415–417CrossRefGoogle Scholar
  22. 22.
    Yuan, C.; Chen, A.; Kolb, P.; Moy, V., Energy landscape of streptavidin-biotin complexes measured by atomic force microscopy. Biochemistry 2000, 39, 10219–10223CrossRefGoogle Scholar
  23. 23.
    Nakamura, C.; Takeda, S.; Kageshima, M.; Ito, M.; Sugimoto, N.; Sekizawa, K.; Miyake, J., Mechanical force analysis of peptide interactions using atomic force microscopy. Biopolymers. 2004, 76, 48–54CrossRefGoogle Scholar
  24. 24.
    Solomon, K.; Bake, D. B.; Richards, R. P.; Dixon, K. R.; Klaine, S. J.; Point, T. W. L.; Kendall, R. J.; Weisskopf, C. P.; Giddings, J. M., About atrazine. Environ. Toxicol. Chem. 1997, 15, 31–76CrossRefGoogle Scholar
  25. 25.
    Wauchope, R. D.; Buttler, T. M.; Hornsby, A. G.; Augustijn-Beckers, P. M. W.; Burt, J. P., Scs/ ars/ces pesticide properties database for environmental decision making. Rev. Environ. Contam. Toxicol. 1992, 123, 1–157Google Scholar
  26. 26.
    Taets, C.; Aref, S.; Rayburn, A. L., The clastogenic potential of triazine herbicide combinations found in potable water supplies. Environ. Health Perspect 1998, 106, 197–201Google Scholar
  27. 27.
    Sathiakumar, N.; Delzell, E., A review of epidemic studies of triazine herbicides and cancer. Crit. Rev. Toxicol. 1997, 27, 599–612CrossRefGoogle Scholar
  28. 28.
    Van Leeuwen, J. A.; Waltner-Toews, D.; Abernathy, T.; Smit, B.; Shoukri, M., Associations between stomach cancer incidence and drinking water contamination with atrazine and nitrate in ontario (canada) agroecosystems, 1987–1991. Int. J. Epidemiol. 1999, 28, 836–840CrossRefGoogle Scholar
  29. 29.
    Chan, W. C.; White, P. D.; Chan, W. C. White, P. D. ed.; Oxford University Press: New York, NY, 2000, pp 41–7630.Google Scholar
  30. 30.
    Eisenberg, D.; Schwarz, E.; Komarony, M.; Wall, R., Amino acid scale: Normalized consensus hydrophobicity scale. J. Mol. Biol. 1984, 179, 125–142.CrossRefGoogle Scholar
  31. 31.
    Obataya, I.; Nakamura, C.; Enomoto, H.; Hoshino, T.; Nakamura, N.; Miyake, J., Development of a herbicide biosensor using a peptide receptor screened from a combinatorial library. J. Mol. Catal. B: Enzym 2004, 28, 265–271CrossRefGoogle Scholar
  32. 32.
    Shan, G.; Leeman, W. R.; Gee, S. J.; Sanborn, J. R.; Jones, A. D.; Chang, D. P. Y.; Hammock, B. D., Highly sensitive dioxin immunoassay and its application to soil and biota samples. Anal. Chim. Acta. 2001, 444, 169–178CrossRefGoogle Scholar
  33. 33.
    Morita, Y.; Murakami, Y.; Yokoyama, K.; Tamiya, E., Synthesis and analysis of peptide ligand for biosensor application using combinatorial chemistry. Biol. Sys. Eng. 2002, (ACS Symposium Series 830), 210–219Google Scholar
  34. 34.
    Nakamura, C.; Inuyama, Y.; Goto, H.; Obataya, I.; Kaneko, N.; Nakamura, N.; Santo, N.; Miyake, J., Dioxin-binding pentapeptide for use in a high-sensitivity on-bead detection assay. Anal. Chem. 2005, 77, 7750–7757CrossRefGoogle Scholar
  35. 35.
    Inuyama, Y.; Nakamura, C.; Oka, T.; Yoneda, Y.; Obataya, I.; Santo, N.; Miyake, J., Simple and high-sensitivity detection of dioxin using dioxin-binding pentapeptide., Biosens. Bioelectron. 2007, 22, 2093–2099CrossRefGoogle Scholar
  36. 36.
    O’Shannessy, D. J.; Brigham-Burke, M.; K., S. K.; Hensley, P.; Brooks, I., Determination of rate and equilibrium binding constants for macromolecular interactions using surface plasmon resonance: Use of nonlinear least squares analysis methods. Anal. Biochem. 1993, 212, 457–468CrossRefGoogle Scholar
  37. 37.
    Roy, S.; Mysior, P.; Brzezinski, R., Comparison of dioxin and furan teq determination in contaminated soil using chemical, micro-erod, and immunoassay analysis., Chemosphere 2002, 48, 833–842CrossRefGoogle Scholar
  38. 38.
    Shimomura, M.; Nomura, Y.; Lee, K. H.; Ikebukuro, K.; Karube, I., Dioxin detection based on immunoassay using a polyclonal antibody against octa-chlorinated dibenzo-p-dioxin (ocdd). Analyst 2001, 126, 1207–1209CrossRefGoogle Scholar
  39. 39.
    Kobayashi, S.; Kitadai, M.; Sameshima, K.; Ishii, Y.; Tanaka, A., A theoretical investigation of the conformation changing of dioxins in binding site of dioxin receptor model; role of absolute hardness-electronegativity diagrams for biological activity. J. Mol. Struct. 1999, 475, 203–217CrossRefGoogle Scholar
  40. 40.
    Procopio, M.; Lahm, A.; Tramontano, A.; Bonati, L.; Pitea, D., A model for recognition of polychlorinated dibenzo-p-dioxins by the aryl hydrocarbon receptor. Eur. J. Biochem. 2002, 269, 13–18CrossRefGoogle Scholar
  41. 41.
    Recinos, A., III; Silvey, K. J.; Ow, D. J.; Jensen, R. H.; Stanker, L. H., Sequences of cDNAs encoding immunoglobulin heavy- and light-chain variable regions from two anti-dioxin monoclonal antibodies. Gene 1994, 149, 385–386CrossRefGoogle Scholar
  42. 42.
    Takahashi, M.; Nokihara, K.; Mihara, H., Construction of a protein-detection system using a loop peptide library with a fluorescence label. Chem. Biol. 2003, 10, 53–60CrossRefGoogle Scholar
  43. 43.
    Wenschuh, H.; Volkmer-Engert, R.; Schmidt, M.; Schulz, M.; Schneider-Mergener, J.; Reineke, U., Coherent membrane supports for parallel microsynthesis and screening of bioactive peptides. Biopolym. (Peptide Sci.) 2000, 55, 188–206CrossRefGoogle Scholar
  44. 44.
    Tseng, M. C.; Chu, Y. H., Using surface plasmon resonance to directly identify molecules in a tripeptide library that bind tightly to a vancomycin chip. Anal. Biochem. 2005, 336, 172–177CrossRefGoogle Scholar

Copyright information

© Springer Science + Business Media, LLC 2009

Authors and Affiliations

  1. 1.Research Institute for Cell EngineeringNational Institute of Advanced Industrial Science and Technology (AIST)IbarakiJapan

Personalised recommendations