SYNTHESIS AND ACTIVITY OF A CYCLO-HEPTAPEPTIDE CONTAINING LYS-GLY-ASP-SEQUENCE AS A NOVEL ANTI-PLATELET AGENT

Jian Jing¹

¹Phone: +86 (010) 5880-2065; fax: +86 (010) 5880-7720; e-mail: [email protected]

Department of Bioorganic and Biological Chemistry, Beijing Key Lab, Beijng Normal University, Beijing, 100875, China

Received March 20, 2013; in final form, April 12, 2013

Linear hepta-peptide Cys-Lys-Gly-Asp-Trp-Asp-Cys was synthesized first and then disulfide bond was formed between the Cys1 and Cys7 to develop cyclo-heptapeptide containing Lys-Gly-Asp-sequence. Structural simulation showed that Lys-Gly-Asp-motif (KDG) displayed functional conformation. The cyclo-heptapeptide exhibited potent anti-platelet aggregation activity based on specific recognition and interaction with the GPIIb-IIIa receptor on platelet cell membrane. The specific and potent anti-platelet activity makes the KGD-containing cyclo-heptapeptide a possible therapeutic agent.

Keywords: KGD-containing cyclo-heptapeptide, platelet aggregation inhibitory activity, integrin binding selectivity.

Биоорг.химия 2013, 39 (5): 547-551