Purification, cloning and biological characterization of a novel disintegrin from Trimeresurus jerdonii venom.
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.
Zhou
Xing-Ding
XD
Kunming Institute of Zoology, the Chinese Academy of Sciences, Kunming 650223 Yunnan, China. zhouxingding@vip.sina.com
Jin
Yang
Y
Chen
Run-Qiang
RQ
Lu
Qiu-Min
QM
Wu
Jian-Bo
JB
Wang
Wan-Yu
WY
Xiong
Yu-Liang
YL
D000595:Amino Acid Sequence; D000818:Animals; D000970:Antineoplastic Agents / Q000302:isolation & purification* / Q000494:pharmacology; D001483:Base Sequence; D002851:Chromatography, High Pressure Liquid; D003001:Cloning, Molecular; D003435:Crotalid Venoms / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification / Q000494:pharmacology; D018076:DNA, Complementary / Q000235:genetics; D019483:Disintegrins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification* / Q000494:pharmacology; D008546:Melanoma, Experimental / Q000188:drug therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000235:genetics / Q000302:isolation & purification* / Q000494:pharmacology; D017385:Sequence Homology; D015996:Survival Rate; D017841:Trimeresurus
D000970:Antineoplastic Agents; D003435:Crotalid Venoms; D018076:DNA, Complementary; D019483:Disintegrins; D009842:Oligopeptides; C029748:Trimeresurus venoms; C485032:jerdonin; C047981:arginyl-glycyl-aspartic acid