High-affinity peptide ligands to prostate-specific antigen identified by polysome selection.

We have used the polysome-selection method to isolate peptide ligands that bind with high affinity to Prostate-Specific Antigen (PSA), an important prostate-cancer marker. Two random libraries, each encoding approximately 10(12) random peptides, were transcribed into RNA and translated in vitro. Polysomes were panned by affinity selection of the nascent peptides against immobilized PSA. Over 30% of the selected species 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 affinities 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.