Cyclic RGD peptide analogues as antiplatelet antithrombotics.

  title={Cyclic RGD peptide analogues as antiplatelet antithrombotics.},
  author={Peter L. Barker and Sherron L. Bullens and Stuart Bunting and Daniel J Burdick and K S Chan and Theresa A. Deisher and Charles Eigenbrot and Thomas R. Gadek and Robin D. Gantzos and Michael T. Lipari},
  journal={Journal of medicinal chemistry},
  volume={35 11},
Stimulation of platelets activates GPIIbIIIa, the heterodimeric integrin receptor, to bind fibrinogen (Fg), which results in platelet aggregation. GPIIbIIIa/Fg binding inhibitors are potentially suitable for acute use during and after thrombolytic therapy as antithrombotic agents. Incorporation of the tripeptide sequence Arg-Gly-Asp (RGD), a common structural element of many integrin ligands, into cyclic peptides produced a series of peptides of the general structure BrAc-(AA1)-RGD-Cys-OH… 
Antithrombotic agents: from RGD to peptide mimetics.
Pharmacophore refinement of gpIIb/IIIa antagonists based on comparative studies of antiadhesive cyclic and acyclic RGD peptides
A classical indirect and comparative pharmacophore refinement approach based on a series of small cyclic Arg-Gly-Asp (RGD) peptides as gpIIb/IIIa-fibrinogen interaction antagonists and several detailed features of the receptor binding site could be deduced in terms of receptor complementarity.
Combinatorial chemistry reveals a new motif that binds the platelet fibrinogen receptor, gpIIbIIIa.
This work used combinatorial chemical and affinity immunochemical methods to find a novel motif of unnatural peptide ligands for the fibrinogen receptor of platelets, gpIIbIIIa (alphaIIbbeta3), and proposes that pi-electrons in the new motif may substitute for the carboxylate group present in all other RGD-types of ligands.
Antagonism of the GPIIb/IIIa receptor with the nonpeptidic molecule BIBU52: inhibition of platelet aggregation in vitro and antithrombotic efficacy in vivo.
BIBU52 is a potent and selective antagonist of the human GPIIb/IIIa receptor and capable of substantial inhibition of platelet aggregation in vitro and ex vivo as well as inhibition of arterial thrombus formation in vivo in animal models of thrombosis.
Synthesis of RGD amphiphilic cyclic peptide as fibrinogen or fibronectin antagonist
The intent was to improve the bioavailability of this new RGD cyclic peptide, which is shown to interact with αIIbβ3 or α5β1 receptors.
A novel series of orally active antiplatelet agents.
Design and synthesis of sulfur-free cyclic hexapeptides which contain the RGD sequence and bind to the fibrinogen GP IIb/IIIa receptor. A conformation-based correlation between propensity for imide formation and receptor affinity.
Three cyclic hexapeptides containing the RGD sequence are designed and synthesized to probe the structural and conformational requirements for potential antithrombotic agents and to identify the distinguishing conformational features of 6, which express themselves both in receptor affinity and chemical propensity toward imide formation.


or an Applied Biosystems Inc. Model 431A or 433A peptide synthesizer. The peptides
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After the initial coupling, the alpha-amino protecting group is removed
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incor porated herein by reference
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