HIGH-AFFINITY PEPTIDE LIGANDS TO PROSTATE-SPECIFIC ANTIGEN IDENTIFIEDBY POLYSOME SELECTION

We have used the polysome-selection method to isolate peptide ligands that bind with high affinity to Prostate-Specific Antigen (PSA), an im portant prostate-cancer marker. Two random libraries, each encoding ap proximately 10(12) random peptides, mere transcribed into RNA and tran slated in vitro. Polysomes were planned by affinity selection of the n ascent peptides against immobilized PSA. Over 30% of the selected spec ies had significant affinity for PSA; the dissociation constant of the complex formed by the best isolate with PSA was < 10(-9) M. Formation of streptavidin conjugates of selected peptides improved their affini ties and, in one case, virtually eliminated non-specific binding. The polysome-selection method can be used to produce high-affinity peptide , ligands of potential use in diagnostic and therapeutic procedures. ( C) 1997 Academic Press.