Development of Novel GPIIB/IIIA Recepetor Antagonist

We will characterize the pharmokinetics of a peptide GPIIb/IIIa receptor antagonist in a caninemodel. Our research has three specific aims. In the first aim, the applicant intends to fully characterizethe pharmokinetics of P246, a 12 residue GPIIb/IIIa receptor antagonist peptide, in a ac dog model.These studies should yield information concerning the clearance, half-life and volume of distribution ofthe peptide in dogs. These studies will be performed in collaboration with Dr. Benedict Lucchesi in theDepartment of Pharmacology at the University of Michigan. In specific Aim 2, the Applicant willexamine the binding kinetics of P246 to a semi-purified human GPIIb/IIIa receptor. These studies willbe performed in collaboration with Dr. Leslie Parise of the UNC School of Medicine and will provideinformation concerning the concentration of peptide or peptides required to half-maximally inhibitfibrinogen binding to these GPIIb/IIIa receptors. In specific Aim 3, the Applicant will continue tosynthesize additional compounds-peptidic and non-peptidic to (a) analog around P246 and (b) identifyeither a backup compound or one with superior properties such as greater potency.