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題 名 | Characterization of Three Endogenous Peptide Inhibitors for Multiple Metalloproteinases with Fibrinogenolytic Activity from the Venom of Taiwan Habu (Trimeresurus Mucrosquamatus) |
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作 者 | Huang,Kai-fa; Hung,Chin-chun; Wu,Shih-hsiung; Chiou,Shyh-horng; | 書刊名 | 中央研究院生物化學研究所論文集 |
卷 期 | 24 1998[民87.] |
頁 次 | 頁89-95 |
分類號 | 361.4 |
關鍵詞 | Multiple metalloproteinases; Fibrinogenolytic activity; Venom; Taiwan habu; |
語 文 | 英文(English) |
英文摘要 | Three small peptide components were isolated, and purified from the venom of Taiwan habu (Trimere- surus mucrosquamatus) which show specific activ- ity to inhibit the strong proteolytic activity of multiple metalloproteinases present in the crude venom. Using multiple chromatographies coupled with successive ultrafiltrations, three inhibitors, i.e. pyroglutamate-lysine-tryptophan (pyroGlu-Lys-Trp) , pyroglutamate-asparagine-tryptophan (pyroGlu-Asn-Trp) and pyroglutamate-glutamine-tryptophan (pyro-Glu-Gln-Trp) were obtained in good yields and high homogeneity. The yields of these peptide fractions were estimated to be about 0.65 mg, 0.55 mg and 0.42 mg from 250 mg total lyophilized crude venom, which corresponded to the approximate concentrations of 8.4 mM, 7.3 mM and 5.4 mM respectively in venom secretion. Detailed and unambiguous structural determination was established by amino acid analyses, mass spectrometry and microsequencing of purified peptides. Further functional characterization of these three tripeptides showed that they could weakly inhibit three metalloproteinases previously isolated from the same venom. The inhibitory activities were similar among these tripeptides and their IC�t (concentration for 50% inhibition) were estimated in a range of 0.20-0.95 mM, which is much more effective than citrate, another venom protease inhibitor of low molecular-weight component. Since these tripeptides are the endogenous peptide inhibitors present in the lumen of venom glands, it is conceivable that they may act as a self-defensive mechanism against the auto-digestive deleterious effect of the strong metalloproteinases in vivo, particularly several zinc-dependent metalloproteinases present in crotalid and viperid venoms. |
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