AUTHOR=Qu Qingrong , Liu Yamin , Yan Xuejiao , Fan Xiaobo , Liu Naifeng , Wu Guoqiu 

TITLE=A Novel Pentapeptide Targeting Integrin β3-Subunit Inhibits Platelet Aggregation and Its Application in Rat for Thrombosis Prevention

JOURNAL=Frontiers in Pharmacology

VOLUME=7

YEAR=2016

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2016.00049

DOI=10.3389/fphar.2016.00049

ISSN=1663-9812

ABSTRACT=<p><bold>Background:</bold> Antiplatelet therapy plays a pivotal role in the prevention and treatment of thrombotic diseases. We reported the screening of P1C as a novel integrin-binding peptide from the C-terminal of connective tissue growth factor. Primary study indicated that P1C has potential against platelet aggregation.</p><p><bold>Objectives:</bold> We aimed to find the shortest active unit from the P1C fragments and explore its <italic>in vivo</italic> and <italic>in vitro</italic> activities.</p><p><bold>Methods:</bold> A series of truncated P1C fragments was prepared and screened for antiplatelet activity. The most active fragment was evaluated using coagulation assays. Flow cytometry and confocal microscopy were used to determine the interaction between the peptide and the integrin. The <italic>in vivo</italic> potential was further explored using two types of rat models.</p><p><bold>Results:</bold> From a series of truncated P1C forms, a so-called P1Cm peptide of 5-amino acids, namely, IRTPK was screened out as the shortest active unit with superior activity. Coagulation experiments and an <italic>in vivo</italic> toxicity assay demonstrated that P1Cm is safe <italic>in vivo</italic> and inhibits ADP- and TH-induced human platelet aggregation <italic>in vitro</italic> in a concentration-dependent manner. Furthermore, it has limited effect on the coagulation parameters. Flow cytometry and confocal microscopy experiments consistently indicated that the peptide specifically binds the β3-subunit of integrin on platelets. Further experiments using rat models of artery-vein shunt and carotid arterial thrombosis illustrated that P1Cm can effectively prevent thrombosis formation.</p><p><bold>Conclusion:</bold> P1Cm may be a new, promising antithrombotic alternative to currently available antiplatelet treatments.</p>