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 IC50 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 EditorThis 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.

Graphical AbstractFour Cu(II) complexes of RGD-octapeptides with different sequence are prepared. The coordination of Cu(II) ions with octapeptides was confirmed by UV-vis and CD spectra, while the 3 N coordination mode of Cu(II) complexes was further characterized by CD/ESI-MS spectra. Transmission electron microscopy measurements of Cu(II) complexes in water in vitro anti-platelet aggregation and in vivo anti-thrombotic assays indicate that the activities of coordination complexes Cu(II) complexes are at most 110-fold and at least 5000-fold higher than that of corresponding octapetides, respectively.Figure optionsDownload high-quality image (376 K)Download as PowerPoint slide