title: Novel Cu(II)-RGD-octapeptides: Synthesis, coordination mode, in vitro anti-platelet aggregation/in vivo anti-thrombotic evaluation and correlation of sequence with nano-structure.
abstract: The synthesis, bioassays and nano-structure characterization of Cu(II)-RGD-octapeptide complexes Cu(II)-Arg-Gly-Asp-Ser-Arg-Gly-Asp-Ser [Cu(II)-4a], Cu(II)-Arg-Gly-Asp-Val-Arg-Gly-Asp-Val [Cu(II)-4b] and Cu(II)-Arg-Gly-Asp-Phe-Arg-Gly-Asp-Phe [Cu(II)-4c] were investigated. UV-vis, CD and CD/ESI-MS spectra suggested that the coordination of Cu(II)-4a-c met a 3 N mode. In the in vitro anti-platelet aggregation assay the IC(50) values of Cu(II)-RGD-octapeptide complexes were 10 - 110 folds lower than that of RGD-octapeptides. In the in vivo anti-thrombotic assay the effective dose of Cu(II)-RGD-octapeptide complexes was 5000 folds lower than that of RGD-octapeptides. In transmission electron microscopy measurement Cu(II)-4a-c offered distinct nano-images. The effect of the sequence on the in vitro anti-platelet aggregation/in vivo anti-thrombotic activity and the nano-structure of Cu(II)-4a-c was discussed.
  
  
  BACKGROUND
  This basic science paper discusses the synthesis, coordination mode, in vitro anti-platelet aggregation and in vivo anti-thrombotic evaluation of novel Cu(II)-RGD-octapeptides.
authors.affiliation: College of Pharmaceutical Sciences, Peking University, Beijing, P.R. China.
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.forename: Guifeng
authors.initials: G
authors.lastname: Kang
authors.forename: Lin
authors.initials: L
authors.lastname: Gui
authors.forename: Ming
authors.initials: M
authors.lastname: Zhao
authors.forename: Wenjing
authors.initials: W
authors.lastname: Wang
authors.forename: Jianwei
authors.initials: J
authors.lastname: Zhang
authors.forename: Yan-Feng
authors.initials: YF
authors.lastname: Yue
authors.forename: Shiqi
authors.initials: S
authors.lastname: Peng
mesh_terms: D000818:Animals; D003300:Copper / Q000737:chemistry*; D008297:Male; D046529:Microscopy, Electron, Transmission; 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*; D051381:Rats; D017208:Rats, Wistar; D013927:Thrombosis / Q000517:prevention & control*
chemical_list: D009842:Oligopeptides; D010975:Platelet Aggregation Inhibitors; D003300:Copper; C047981:arginyl-glycyl-aspartic acid