Effects of amino acid substitutions in and around the arginine-glycine-aspartic acid (RGD) sequence on fertilization and parthenogenetic development in mature bovine oocytes.
Integrins have been shown to be involved in the process of fertilization and many integrin-ligand interactions are mediated through the recognition of an arginine-glycine-aspartic acid (RGD) sequence. Despite the fact the RGD domain is a principal player in determining the functional characteristics of an adhesive protein, increasing evidence has accumulated implicating the amino acids flanking the RGD sequence in determining the functional properties of the RGD-containing protein. A set of linear peptides in which the amino acid sequence in and around the RGD tri-peptide was modified was synthesized to better understand the specificity of the RGD-receptor interaction. Mature oocytes were fertilized in vitro in the presence of RGD-containing and RGD-modified peptides. Both the RGD-containing and RGD-modified peptides impaired the ability of sperm to fertilize bovine oocytes, illustrated by a reduction in cleavage. The linear modified RGD containing peptides were also examined for their ability to induce parthenogenetic development with the objective of providing a linear RGD peptide with greater biological activity than the one (GRGDSPK) used previously (Campbell et al., 2000). The data demonstrate the specificity of the receptor for the RGD sequence, further implicate the involvement of integrins in the process of bovine fertilization, and illustrate the importance of the amino acids surrounding the RGD sequence in determining the binding and functional properties of RGD-containing peptides. The data support the findings that a linear RGD peptide can block fertilization and that amino acids around the RGD sequence have an impact on the biological activity of the receptor.
Sessions
B R
BR
Department of Animal, Dairy, and Veterinary Sciences and Center for Integrated Biosystems, Utah State University, Logan, Utah, USA.
Aston
K I
KI
Davis
A P
AP
Pate
B J
BJ
White
K L
KL
D019943:Amino Acid Substitution; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002417:Cattle; D002970:Cleavage Stage, Ovum / Q000187:drug effects / Q000502:physiology; D005260:Female; D005307:Fertilization in Vitro; D016023:Integrins / Q000819:agonists* / Q000378:metabolism; D008297:Male; D009842:Oligopeptides / Q000235:genetics / Q000494:pharmacology*; D009865:Oocytes / Q000166:cytology / Q000502:physiology*; D010312:Parthenogenesis / Q000187:drug effects* / Q000502:physiology; D013084:Sperm-Ovum Interactions / Q000187:drug effects
D000970:Antineoplastic Agents; D016023:Integrins; D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid