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Generation and use of synthetic peptide combinatorial libraries for basic research and drug discovery

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Abstract

EXISTING methods for the synthesis and screening of large numbers of peptides are limited by their inability to generate and screen the requisite number (millions) of individual peptides1–4 and/or their inability to generate unmodified free peptides in quantities able to interact in solution4–8. We have circumvented these limitations by developing synthetic peptide combinatorial libraries composed of mixtures of free peptides in quantities which can be used directly in virtually all existing assay systems. The screening of these heterogeneous libraries, along with an iterative selection and synthesis process, permits the systematic identification of optimal peptide ligands. Starting with a library composed of more than 34 million hexa-peptides, we present here the precise identification of an antigenic determinant recognized by a monoclonal antibody as well as the straightforward development of new potent antimicrobial peptides.

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Authors and Affiliations

  1. Torrey Pines Institute for Molecular Studies, 3550 General Atomics Court, San Diego, California, 92121, USA

    Richard A. Houghten, Clemencia Pinilla, Sylvie E. Blondelle, Jon R. Appel, Colette T. Dooley & Julio H. Cuervo

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  1. Richard A. Houghten
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  2. Clemencia Pinilla
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  3. Sylvie E. Blondelle
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  4. Jon R. Appel
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  5. Colette T. Dooley
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  6. Julio H. Cuervo
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Houghten, R., Pinilla, C., Blondelle, S. et al. Generation and use of synthetic peptide combinatorial libraries for basic research and drug discovery. Nature 354, 84–86 (1991). https://doi.org/10.1038/354084a0

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  • DOI: https://doi.org/10.1038/354084a0

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