Efficient targeted anticoagulant with active RGD motif.
Three anticoagulants combining large peptide recombinant hirudin variants (rHV2-K47) and Arg-Gly-Asp (RGD) motif related to platelet aggregation were generated, i.e. sequences CRFPRGDADPYCE and CNPRGDFRCI were added to the C-terminus of hirudin to obtain RGD-hirudin 1 and 2, respectively, and the sequence RGDSE was inserted between residues 53-54 of hirudin to obtain RGD-hirudin 3. All products exhibited antithrombin and antiplatelet activities, especially IC50 of RGD-hirudin 1 and 2 were much lower with respect to previously reported similar peptides. Our data suggested that RGD-hirudin 1 and 2 would be promising anticoagulants in clinic. Moreover, the triangular structure of active RGD was shown by computer simulation, which might contribute to our understanding on integrin-related peptides and proteins.
Bi
Qun
Q
National Key Laboratory of Biomembrane and Membrane Biotechnology, College of Life Sciences, Peking University, Beijing, 100871, PR China.
Zhou
Xue
X
Cen
Xiaodong
X
Qu
Hong
H
Luo
Jingchu
J
Huang
Yixiu
Y
Zhu
Shenggeng
S
D000595:Amino Acid Sequence; D000925:Anticoagulants / Q000737:chemistry* / Q000494:pharmacology*; D003198:Computer Simulation; D016503:Drug Delivery Systems; D006629:Hirudins / Q000235:genetics*; D006801:Humans; D009842:Oligopeptides / Q000235:genetics*; D010974:Platelet Aggregation / Q000187:drug effects; D011487:Protein Conformation; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013917:Thrombin / Q000378:metabolism
D000925:Anticoagulants; D006629:Hirudins; D009842:Oligopeptides; D011993:Recombinant Fusion Proteins; C047981:arginyl-glycyl-aspartic acid; D013917:Thrombin