Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

A new type of synthetic peptide library for identifying ligand-binding activity

A Correction to this article was published on 31 December 1992

A Correction to this article was published on 30 July 1992

Abstract

OUR aim was to improve techniques for drug development by facilitating the identification of small molecules that bind with high affinity to acceptor molecules (for example, cell-surface receptors, enzymes, antibodies) and so to mimic or block their interaction with the natural ligand1,2. Previously such small molecules have been characterized individually on a serial basis. The systematic synthesis and screening of peptide libraries of defined structure represents a new approach. For relatively small libraries, predetermined sequence variations on solid-phase supports have been used3,4, and large libraries have been produced using a bacteriophage vector into which random oligodeoxynucleotide sequences have been introduced5–8, but these techniques have severe limitations. Here we investigate an alternative approach to synthesis and screening of peptide libraries. Our simple methodology greatly enhances the production and rapid evaluation of random libraries of millions of peptides so that acceptor-binding ligands of high affinity can be rapidly identified and sequenced, on the basis of a "one-bead, one-peptide9 approach.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

References

  1. Hruby, V. J., Al-Obeidi, F. & Kazmierski, W. Biochem. J. 268, 246–262 (1990).

    Article  Google Scholar 

  2. Hruby, V. J. & Sharma, S. D. Curr. Opin. Biotech. 2, 599–605 (1991).

    Article  CAS  Google Scholar 

  3. Geysen, H. M., Melven, R. H. & Barteling, S. J. Proc. natn. Acad. Sci. U.S.A. 81, 3998–4002 (1984).

    Article  ADS  CAS  Google Scholar 

  4. Fodor, S. P. et al. Science 251, 767–773 (1991).

    Article  ADS  CAS  Google Scholar 

  5. Parmley, S. F. & Smith, G. P. Gene 73, 305–318 (1988).

    Article  CAS  Google Scholar 

  6. Scott, J. K. & Smith, G. P. Science 249, 386–390 (1990).

    Article  ADS  CAS  Google Scholar 

  7. Cwirla, S. E., Peters, E. A., Barrett, R. W. & Dower, W. J. Proc. natn. Acad. Sci. U.S.A. 87, 6378–6382 (1990).

    Article  ADS  CAS  Google Scholar 

  8. Devlin, J. J., Panganiban, L. C. & Devlin, P. E. Science 249, 404–406 (1990).

    Article  ADS  CAS  Google Scholar 

  9. Niall, H. D., Tregear, G. W. & Jacobs, J. in Chemistry and Biology of Peptides, (ed. Meienhofer, J.), 695 (Ann Arbor, Michigan, 1972).

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lam, K., Salmon, S., Hersh, E. et al. A new type of synthetic peptide library for identifying ligand-binding activity. Nature 354, 82–84 (1991). https://doi.org/10.1038/354082a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/354082a0

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing