title: Design, synthesis of novel tryptophan derivatives for antiplatelet aggregation activity based on tripeptide pENW (pGlu-Asn-Trp).
abstract: pENW, a three mer peptide derived from Agkistrodon acutus Guenther venom, has been found to be an antagonist of the GPIIb/IIIa receptor and shows antiplatelet aggregation activity. Based on pENW and a GPIIb/IIIa inhibitor Tirofiban, a series of tryptophan derivatives were designed, synthesized and evaluated for their antiplatelet aggregation activity induced by ADP. The most potent compound 87 was also tested for the bleeding time and antithrombotic activity in vivo in comparison with Tirofiban. The results indicated that 87 shows similar antiplatelet aggregation activity as Tirofiban to the aggregation of platelet induced by all of the four agonists, but has lower bleeding risk than Tirofiban, representing a promising lead compound for further study.
authors: Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 21009, PR China.
authors: Zhouling
authors: Z
authors: Xie
authors: Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 21009, PR China.
authors: Sen
authors: S
authors: Feng
authors: School of Life Science & Technology, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China.
authors: Ying
authors: Y
authors: Wang
authors: Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 21009, PR China.
authors: Chen
authors: C
authors: Cao
authors: Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 21009, PR China.
authors: Jing
authors: J
authors: Huang
authors: School of Life Science & Technology, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China.
authors: Yahui
authors: Y
authors: Chen
authors: School of Life Science & Technology, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China. Electronic address: yikong668@163.com.
authors: Yi
authors: Y
authors: Kong
authors: Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 21009, PR China. Electronic address: zhiyuli@cpu.edu.cn.
authors: Zhiyu
authors: Z
authors: Li
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D015394:Molecular Structure; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011817:Rabbits; D013329:Structure-Activity Relationship
chemical_list: D009842:Oligopeptides; D010975:Platelet Aggregation Inhibitors; C114010:pyroglutamyl-asparagyl-tryptophan; D011761:Pyrrolidonecarboxylic Acid
keywords: Antiplatelet aggregation; Bleeding risk; GPIIb/IIIa receptor inhibitor; Tryptophan derivatives; pENW