Discovery of biologically active peptides in random libraries: Solution-phase testing after staged orthogonal release from resin beads

Sydney E. Salmon, Kit Lam, Michal Lebl, Anitha Kandola, Parth S. Khattri, Shelly Wade, Marcel Pátek, Petr Kocis, Viktor Krchnák, David Thorpe, Stephen Felder

Research output: Contribution to journalArticle

123 Citations (Scopus)

Abstract

To speed drug discovery, we developed an approach for identification of individual peptides with a desired biological activity from a library containing millions of peptides. The approach uses sequential orthogonal release of chemically synthesized peptides from insoluble beads, followed by testing in solution. In this system, each bead within a library of beads has one peptide sequence, but peptide molecules are attached to the bead with three types of chemical linkers, including two linkers cleavable at different pH optima. An uncleavable linker keeps some peptide attached to the bead for sequencing positives from the solution assay. Applicability of this discovery technique was documented by identifying ligands for a monoclonal antibody and for the human platelet fibrinogen receptor, glycoprotein IIb/IIIa.

Original languageEnglish (US)
Pages (from-to)11708-11712
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume90
Issue number24
StatePublished - Dec 15 1993
Externally publishedYes

Fingerprint

Peptide Library
Peptides
Libraries
Fibrinogen Receptors
Platelet Glycoprotein GPIIb-IIIa Complex
Drug Discovery
Blood Platelets
Monoclonal Antibodies
Ligands

Keywords

  • Peptide library screening

ASJC Scopus subject areas

  • General
  • Genetics

Cite this

Discovery of biologically active peptides in random libraries : Solution-phase testing after staged orthogonal release from resin beads. / Salmon, Sydney E.; Lam, Kit; Lebl, Michal; Kandola, Anitha; Khattri, Parth S.; Wade, Shelly; Pátek, Marcel; Kocis, Petr; Krchnák, Viktor; Thorpe, David; Felder, Stephen.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 90, No. 24, 15.12.1993, p. 11708-11712.

Research output: Contribution to journalArticle

Salmon, SE, Lam, K, Lebl, M, Kandola, A, Khattri, PS, Wade, S, Pátek, M, Kocis, P, Krchnák, V, Thorpe, D & Felder, S 1993, 'Discovery of biologically active peptides in random libraries: Solution-phase testing after staged orthogonal release from resin beads', Proceedings of the National Academy of Sciences of the United States of America, vol. 90, no. 24, pp. 11708-11712.
Salmon, Sydney E. ; Lam, Kit ; Lebl, Michal ; Kandola, Anitha ; Khattri, Parth S. ; Wade, Shelly ; Pátek, Marcel ; Kocis, Petr ; Krchnák, Viktor ; Thorpe, David ; Felder, Stephen. / Discovery of biologically active peptides in random libraries : Solution-phase testing after staged orthogonal release from resin beads. In: Proceedings of the National Academy of Sciences of the United States of America. 1993 ; Vol. 90, No. 24. pp. 11708-11712.
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