Journal Article

Discovery of Biologically Active Peptides in Random Libraries: Solution- Phase Testing After Staged Orthogonal Release from Resin Beads

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

1993

Overview

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.

• Publisher: National Academy of Sciences of the United States of America,National Acad Sciences,National Academy of Sciences
• Subject: Amino Acid Sequence / Amino acids / Antibodies, Monoclonal - metabolism / beta-Endorphin - immunology / Biological and medical sciences / Chemistry / Diverse techniques / Enzyme-Linked Immunosorbent Assay / Enzymes / Esters / Fundamental and applied biological sciences. Psychology / Humans / Libraries / Ligands / Molecular and cellular biology / Molecular Sequence Data / Molecular structure / Molecules / Monoclonal antibodies / Oligopeptides - chemical synthesis / Oligopeptides - chemistry / Oligopeptides - pharmacology / Peptides / Peptides - chemical synthesis / Peptides - chemistry / Peptides - pharmacology / Platelet Membrane Glycoproteins - immunology / Protein Conformation / Proteins / Receptors / Resins