Inhibition of platelet adhesion by peptidomimetics mimicking the interactive β-hairpin of glycoprotein Ibα

Elise Bernard; Vivienne Buckley; Edelmiro Moman; Lorraine Coleman; Gerardene Meade; Dermot Kenny; Marc Devocelle

doi:10.1016/j.bmcl.2012.03.022

Inhibition of platelet adhesion by peptidomimetics mimicking the interactive β-hairpin of glycoprotein Ibα

Bioorg Med Chem Lett. 2012 May 1;22(9):3323-6. doi: 10.1016/j.bmcl.2012.03.022. Epub 2012 Mar 11.

Authors

Elise Bernard¹, Vivienne Buckley, Edelmiro Moman, Lorraine Coleman, Gerardene Meade, Dermot Kenny, Marc Devocelle

Affiliation

¹ Centre for Synthesis & Chemical Biology, Department of Pharmaceutical & Medicinal Chemistry, 123, St. Stephen's Green, Dublin 2, Ireland.

PMID: 22460035
DOI: 10.1016/j.bmcl.2012.03.022

Abstract

β-Hairpin peptidomimetics mimicking the interaction sites of the platelet receptor glycoprotein (GP)Ibα with von Willebrand factor (vWF) were synthesised and evaluated for their ability to increase platelet velocity under high shear conditions and to inhibit shear-induced platelet aggregation. A cyclic and bridged dodecapeptide 2e containing a heterochiral diproline motif was identified as a lead compound for the generation of a novel class of potential antiplatelet agents.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Binding Sites
Humans
Peptidomimetics / chemistry
Peptidomimetics / pharmacology*
Platelet Adhesiveness / drug effects*
Platelet Aggregation / drug effects
Platelet Aggregation Inhibitors / chemistry*
Platelet Glycoprotein GPIb-IX Complex / chemistry*
Platelet Glycoprotein GPIb-IX Complex / metabolism
Protein Binding
Protein Structure, Secondary
von Willebrand Factor / chemistry
von Willebrand Factor / metabolism

Substances

Peptidomimetics
Platelet Aggregation Inhibitors
Platelet Glycoprotein GPIb-IX Complex
von Willebrand Factor