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从竹叶青蛇毒液中纯化、克隆并鉴定一种新型去整合素的生物学特性

Purification, cloning and biological characterization of a novel disintegrin from Trimeresurus jerdonii venom.

作者信息

Zhou Xing-Ding, Jin Yang, Chen Run-Qiang, Lu Qiu-Min, Wu Jian-Bo, Wang Wan-Yu, Xiong Yu-Liang

机构信息

Kunming Institute of Zoology, the Chinese Academy of Sciences, Kunming 650223 Yunnan, China.

出版信息

Toxicon. 2004 Jan;43(1):69-75. doi: 10.1016/j.toxicon.2003.10.023.

DOI:10.1016/j.toxicon.2003.10.023
PMID:15037031
Abstract

A novel disintegrin, jerdonin, was purified from the Trimeresurus jerdonii venom by means of gel filtration and reverse phase high pressure liquid chromatography. Its coding cDNA was also isolated from the venom gland. The jerdonin coding cDNA is part of a precursor composed of proprotein, metalloproteinase, and disintegrin domains. From the deduced amino acid sequence, jerdonin is composed of 71 amino acid residues including 12 cysteines and the tripeptide sequence Arg-Gly-Asp (RGD), a well-known characteristic of the disintegrin family. Molecular mass of jerdonin was determined to be 7483Da by matrix-assisted laser desorption ionization time of flight mass spectrometry. Jerdonin inhibited ADP- and collagen-induced human platelet aggregation with IC(50) of 220 and 240 nM, respectively. In vivo, jerdonin inhibited the growth of subcutaneously inoculated B16 solid tumor in C57BL/6 mice and improved the survival time of the tumor-bearing mice.

摘要

一种新型的去整合素——竹叶青蛇毒素(jerdonin),通过凝胶过滤和反相高压液相色谱法从竹叶青蛇(Trimeresurus jerdonii)毒液中纯化得到。其编码cDNA也从毒腺中分离出来。竹叶青蛇毒素编码cDNA是由前体蛋白、金属蛋白酶和去整合素结构域组成的前体的一部分。根据推导的氨基酸序列,竹叶青蛇毒素由71个氨基酸残基组成,包括12个半胱氨酸以及三肽序列精氨酸-甘氨酸-天冬氨酸(Arg-Gly-Asp,RGD),这是去整合素家族的一个众所周知的特征。通过基质辅助激光解吸电离飞行时间质谱法测定,竹叶青蛇毒素的分子量为7483Da。竹叶青蛇毒素抑制二磷酸腺苷(ADP)和胶原诱导的人血小板聚集,其半数抑制浓度(IC50)分别为220和240 nM。在体内,竹叶青蛇毒素抑制C57BL/6小鼠皮下接种的B16实体瘤的生长,并延长荷瘤小鼠的存活时间。

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