STRUCTURAL AND MECHANISTIC DETERMINANTS OF AFFINITY AND SPECIFICITY OF LIGANDS DISCOVERED OR ENGINEERED BY PHAGE DISPLAY

The scope and utility of phage display is reviewed with emphasis on me dical applications and structure-based ligand and drug design, from li terature mostly after 1994. General principles by which phage-displaye d peptides achieve affinity and selectivity for targets are described, along with selected structural or mechanistic studies of the binding of peptides or proteins discovered or engineered by phage display. Suc h engineered proteins whose wild-type or mutant crystal or 2D-NMR stru ctures yield insight about the basis for enhanced affinity or altered specificity include antibodies, zinc fingers, human growth hormone, pr otein A, and atrial natriuretic peptide. Structures of complexes of de novo phage-discovered peptide ligands with targets such as the Src SH 3 domain, streptavidin, and erythropoietin receptor reveal the structu ral basis for receptor-peptide recognition in these systems.