| Title | Synthesis, nano-scale assembly, and in vivo anti-thrombotic activity of novel short peptides containing L-Arg and L-Asp or L-Glu |
| Authors | Chen, Yu Cui, Guohui Zhao, Ming Wang, Chao Qian, Keduo Morris-Natschke, Susan Lee, Kuo-Hsiung Peng, Shiqi |
| Affiliation | Capital Med Univ, Coll Pharmaceut Sci, Beijing 100069, Peoples R China. Peking Univ, Coll Pharmaceut Sci, Beijing 100083, Peoples R China. Univ N Carolina, Sch Pharm, Nat Prod Res Labs, Chapel Hill, NC 27599 USA. |
| Keywords | Asp-Arg-peptides Glu-Arg-peptides Cu(II)-complex synthesis self-assembling anti-thrombotic activity PLATELET-AGGREGATION DISEASE FABRICATION INHIBITION MECHANISMS THROMBOSIS NANOTUBES PROTEINS FIBERS |
| Issue Date | 2008 |
| Publisher | 生物有机化学与医药化学 |
| Citation | BIOORGANIC & MEDICINAL CHEMISTRY.2008,16,(11),5914-5925. |
| Abstract | Two tripeptides H-Asp(Arg)-Arg (3a) and H-Glu(Arg)-Arg (3b), four pentapeptides H-Asp(Arg-Asp)-Arg-Asp (6a), H-Glu(Arg-Asp)-Arg-Asp (6b), H-Asp(Asp-Arg)-Asp-Arg (10a), and H-Glu(Asp-Arg)-Asp-Arg (10b), and their Cu(II)-peptide complexes Cu(II)-Asp(Arg)-Arg [3a-Cu(II)], Cu(II)-Glu(Arg)-Arg [3b-Cu(II)], Cu(II)-Asp(Arg-Asp)-Arg-Asp [6a-Cu(II)], Cu(II)-Glu(Arg-Asp)-Arg-Asp [6b-Cu(II)], Cu(II)-Asp(Asp-Arg)-Asp-Arg [10a-Cu(II)], and Cu(II)-Glu(Asp-Arg)-Asp-Arg [10b Cu( II)] were designed and synthesized. Their self-assembling properties and in vivo anti-thrombotic activities were investigated. In normal saline (NS), the Cu(II)-peptide complexes assembled into stable nano-particles surrounded by negative charges (-4.102 to -9.825 mV), with diameters ranging from 212.1 +/- 4.0 to 632.4 +/- 36.7 nm. TEM analysis exhibited that the compounds remained as nano-globes in the solid state, with diameters ranging from 15 to 20 nm. In an in vivo anti-thrombotic assay, peptides (3,6,10) a, b at 5 mu mol/kg reduced the thrombus weights of a rat model by 15-40%. Aspirin, a widely used anti-thrombotic drug, achieved comparable activity in this model system at a dosage of ca. 110 mu mol/kg. The required dosage of Cu(II)-peptide complexes [(3,6,10) a, b]-Cu(II), which assemble into stable nano-particles, was significantly reduced to 0.05 mu mol/kg. Therefore, the antithrombotic activity of the nano-particles [(3,6,10) a, b] -Cu(II) increased dramatically by 100-fold over that of the corresponding peptides. (C) 2008 Elsevier Ltd. All rights reserved. |
| URI | http://hdl.handle.net/20.500.11897/197947 |
| ISSN | 0968-0896 |
| DOI | 10.1016/j.bmc.2008.04.064 |
| Indexed | SCI(E) PubMed |
| Appears in Collections: | 药学院 |
