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

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. From the Clinical Editor: 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. Crown Copyright (C) 2011 Published by Elsevier Inc. All rights reserved.