SCANNING WHOLE CELLS WITH PHAGE-DISPLAY LIBRARIES - IDENTIFICATION OF PEPTIDE LIGANDS THAT MODULATE CELL-FUNCTION

A general strategy has been developed for rapidly identifying peptides that alter cellular function, which has revealed a series of peptides that inhibit platelet aggregation. First whole cells-platelets in this case-were used as an affinity matrix to isolate cell-binding phage from a phage-display, random-peptide library. In this step 3 x 10(7) different filamentous phage, each encoding and displaying a different random peptide, were screened as a single pool. Since it is the peptide displayed on the surface of the phage that presumably causes a particular phage to bind specifically to a cell, synthetic peptides were then made based on the predicted sequences of the displayed peptides. Because the initial affinity selection step had focused attention on a handful of peptides, each of the 17 synthetic peptides could be individually tested in an appropriate functional assay, such as platelet aggregation. The majority of the 17 different peptides that we analyzed inhibited platelet aggregation; these peptides could be grouped into at least five different motifs including the expected RGD motif. It is believed that this strategy, which requires neither purification nor prior knowledge of a particular target receptor, will prove to be generally useful for identifying peptide ligands that influence cellular function. (C) 1994 Wiley-Liss, Inc.