Selection of peptides targeting the human sperm surface using random peptide phage display identify ligands homologous to ZP3

Analysis of the surface architecture of human spermatozoa is a necessary st ep in the development of new approaches to contraception and resolving the causes of human infertility, In this study we have utilized phage display t echnology to identify peptides that bind with high affinity to the surface of human spermatozoa. Fifteen- and twelve-mer random peptide phage display libraries were screened against paraformaldehyde-fixed spermatozoa and a nu mber of sperm-binding peptides were identified. One peptide, M6, displayed a high level of affinity for the sperm surface and showed sequence homology with a dominant human ZP3 epitope (hZP 25-33), This peptide bound preferen tially to the equatorial and post acrosomal domains of the sperm head and e xhibited contraceptive activity by virtue of its capacity to impair the fus ion of acrosome-reacted spermatozoa with the vitelline membrane of the oocy te, A similar form of contraceptive activity was also observed within an un related peptide, K6, derived from screening the 12-mer library. These resul ts indicate that phage display technology is a powerful tool for developing reagents capable of targeting the human sperm surface, providing insights into the composition of this structure and the identity of targets suscepti ble to contraceptive attack and pathological disruption.