Open AccessDiscovery of biologically active peptides in random libraries: solution-phase testing after staged orthogonal release from resin beads.
Author(s) -
Sydney E. Salmon,
Kit S. Lam,
Michal Lebl,
A. Kandola,
P. S. Khattri,
Shelly Wade,
Marcel Pátek,
Petr Kočiš,
Viktor Krchňák,
David Thorpe
Publication year - 1993
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.90.24.11708
Subject(s) - linker , peptide , combinatorial chemistry , peptide library , chemistry , cyclic peptide , drug discovery , peptide sequence , biochemistry , computer science , gene , operating system
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.