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Thromb Haemost 1989; 61(02): 183-188
DOI: 10.1055/s-0038-1646556
Original Article
Schattauer GmbH Stuttgart

Demonstration of Ac-Arg-Gly-Asp-Ser-NH2 as an Antiaggregatory Agent in the Dog by Intracoronary Administration

R J Shebuski
1   The Department of Pharmacology, Smith Kline & French Laboratories, King of Prussia, PA, USA
,
D E Berry
2   The Department of Biomolecular Discovery, Smith Kline & French Laboratories, King of Prussia, PA, USA
,
D B Bennett
2   The Department of Biomolecular Discovery, Smith Kline & French Laboratories, King of Prussia, PA, USA
,
T Romoff
3   The Department of Peptide Chemistry, Smith Kline & French Laboratories, King of Prussia, PA, USA
,
B L Storer
1   The Department of Pharmacology, Smith Kline & French Laboratories, King of Prussia, PA, USA
,
F Ali
3   The Department of Peptide Chemistry, Smith Kline & French Laboratories, King of Prussia, PA, USA
,
J Samanen
3   The Department of Peptide Chemistry, Smith Kline & French Laboratories, King of Prussia, PA, USA
› Author Affiliations
Further Information

Publication History

Received 03 August 1988

Accepted after revision 23 November 1988

Publication Date:
30 June 2018 (online)

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Summary

This study compared the anti-platelet effect of Ac-RGDS-NH2 which is a peptide fragment from fibrinogen to Ac-RGES-NH2 in which the aspartic acid (D) of Ac-RGDS-NH2 has been replaced by glutamic acid (E). When Ac-RGDS-NH2 was infused intracoronary at concentrations of 100–400 mM, acute platelet dependent thrombus formation in the dog coronary artery was inhibited. However, infusion of Ac-RGES-NH2 intracoronary at similar concentrations to Ac-RGDS-NH2 failed to inhibit platelet dependent thrombus formation in the dog. Ac-RGDS-NH2 and Ac-RGES-NH2 were also tested for their ability to inhibit collagen-induced platelet aggregation in vitro. Ac-RGDS-NH2 elicited concentration-dependent inhibition of collagen-induced aggregation with no effect of Ac-RGES-NHz otr collagen-induced platelet aggregation. Thus, Ac-RGDS-NH2 is an effective antiplatelet agent after intracoronary administration in the dog and also inhibits collagen-induced platelet aggregation in vitro. Ac-RGDS-NH2 is a specific inhibitor of platelet aggregation as replacement of the aspartic acid in Ac-RGDS-NH2 with glutamic acid results in complete loss of biological activity.

Keywords

Fibrinogen receptor antagonists - Platelet aggregation - Ac-RGDS-NH2 - Coronary artery - Canine
 

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