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The effect of complexation of Cu(II) with P6A peptide and its analogs on their thrombolytic activities
Yang, Mei2; Cui, Guohui1; Zhao, Ming1; Wang, Chao2; Wang, Lili1,3; Liu, Hu1,3,4; Peng, Shiqi1,2
关键词Cu(II)-peptide complex Self-assembly Thrombolytic activity
刊名INTERNATIONAL JOURNAL OF PHARMACEUTICS
2008-10-01
DOI10.1016/j.ijpharm.2008.06.014
362期:1-2页:81-87
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Pharmacology & Pharmacy
研究领域[WOS]Pharmacology & Pharmacy
关键词[WOS]DEGRADATION PRODUCT PEPTIDE-6A ; COPPER(II) COMPLEXES ; BLOOD-FLOW ; CU(II)-DIPEPTIDE COMPLEXES ; PLASMINOGEN-ACTIVATOR ; CRYSTAL-STRUCTURES ; BINDING ; PENTAPEPTIDE ; PERSPECTIVES ; METABOLITES
英文摘要

The complexation of Cu(II) with previously synthesized thrombolytic peptides, Pro-Ala-Lys (6), Arg-Pro-Ala-Lys (7), Ala-Arg-Pro-Ala-Lys (8), Gly-Arg-Pro-Ala-Lys (9) and Gln-Arg-Pro-Ala-Lys (10), resulted in the formation of complexes, Cu(II)-(Pro-Ala-Lys) (6-Cu), Cu(II)-(Arg-Pro-Ala-Lys) (7-Cu), Cu(II)-(Ala-Arg-Pro-Ala-Lys) (8-Cu), Cu(II)-(Gly-Arg-Pro-Ala-Lys) (9-Cu) and Cu(II)-(Gln-Arg-Pro-Ala-Lys) (10-Cu), which was confirmed by UV-Vis, circular dichroism and ESI-MS analyses. Complexes (6-10)-Cu in normal saline (NS) were found to be able to assemble into aggregates, and the size of the aggregates were measured for the next eight consecutive days. It was found that on the 8th day, the diameters of (6-10)-Cu aggregates ranged from 179.21 +/- 38.33 nm to 293.46 +/- 51.07 mn. The Zeta potentials of (6-10)-Cu aggregates in NS were also examined and it was found that aggregates of (6, 8, 10)-Cu were negatively charged, and 7-Cu and 9-Cu were positively charged. The powders of (6-10)-Cu were analyzed by transmission electron microscopy and were found to have mean particle sizes of 8-15 nm. The in vitro euglobulin lysis, vasodilation and thrombolytic assays indicated that complexation With Cu(II) resulted in a significant increase in the activities of 6-10. The in vivo thrombolytic assays revealed that complexation with Cu(II) resulted in a significant enhancement in the in vivo thrombolytic activities for 6, 7,8 and 10 at 10 mu mol/kg, and 9 at 1 mu mol/kg and 0.1 mu mol/kg, respectively. These findings suggested that the self-assembly of the Cu(II)-peptide complexes into nano-scale aggregates was beneficial in improving the thrombolytic activity of the peptides. (C) 2008 Elsevier B.V. All rights reserved.

语种英语
WOS记录号WOS:000263080700013
项目编号2006CB708501 ; 20772082
资助机构Beijing Key Laboratory Program ; Small Molecular Drugs ; 973 Project of China ; Natural Scientific Foundation of China
引用统计
被引频次:7[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/60796
专题北京大学药学院
作者单位1.Capital Med Univ, Coll Pharmaceut Sci, Beijing 100069, Peoples R China
2.Peking Univ, Coll Pharmaceut Sci, Beijing 100083, Peoples R China
3.Mem Univ Newfoundland, Sch Pharm, St John, NF A1B 3V6, Canada
4.Mem Univ Newfoundland, Fac Sci, Dept Biochem, St John, NF A1B 3V6, Canada
推荐引用方式
GB/T 7714
Yang, Mei,Cui, Guohui,Zhao, Ming,et al. The effect of complexation of Cu(II) with P6A peptide and its analogs on their thrombolytic activities[J]. INTERNATIONAL JOURNAL OF PHARMACEUTICS,2008,362(1-2):81-87.
APA Yang, Mei.,Cui, Guohui.,Zhao, Ming.,Wang, Chao.,Wang, Lili.,...&Peng, Shiqi.(2008).The effect of complexation of Cu(II) with P6A peptide and its analogs on their thrombolytic activities.INTERNATIONAL JOURNAL OF PHARMACEUTICS,362(1-2),81-87.
MLA Yang, Mei,et al."The effect of complexation of Cu(II) with P6A peptide and its analogs on their thrombolytic activities".INTERNATIONAL JOURNAL OF PHARMACEUTICS 362.1-2(2008):81-87.
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