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 step in the development of new approaches to contraception and resolving the causes of human infertility. In this study we have utilized phage display technology 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 number 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 preferentially to the equatorial and post acrosomal domains of the sperm head and exhibited contraceptive activity by virtue of its capacity to impair the fusion of acrosome-reacted spermatozoa with the vitelline membrane of the oocyte. A similar form of contraceptive activity was also observed within an unrelated peptide, K6, derived from screening the 12-mer library. These results 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 susceptible to contraceptive attack and pathological disruption.
Eidne
K A
KA
Western Australian Institute for Medical Research & Keogh Institute for Medical Research, QEII Medical Centre, Nedlands, Perth 6009, Australia. keidne@waimr.uwa.edu.au
Henery
C C
CC
Aitken
R J
RJ
D000328:Adult; D017104:Bacteriophage M13 / Q000235:genetics; D001434:Bacteriophage Typing; D002459:Cell Fusion; D018914:Cells, Immobilized; D003001:Cloning, Molecular; D004527:Egg Proteins / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D006562:Herpes Zoster; D006801:Humans; D066298:In Vitro Techniques; D008024:Ligands; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D009865:Oocytes / Q000502:physiology; D010455:Peptides / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D011956:Receptors, Cell Surface; D013094:Spermatozoa / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D000072216:Zona Pellucida Glycoproteins
D004527:Egg Proteins; D008024:Ligands; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D010455:Peptides; D011956:Receptors, Cell Surface; C000606517:ZP3 protein, human; D000072216:Zona Pellucida Glycoproteins