PHARMACOLOGICAL ACTIVITY OF THE INTERDOMAIN SEGMENT BETWEEN METALLOPROTEINASE AND DISINTEGRIN DOMAINS

Citation
Rm. Kini et al., PHARMACOLOGICAL ACTIVITY OF THE INTERDOMAIN SEGMENT BETWEEN METALLOPROTEINASE AND DISINTEGRIN DOMAINS, Toxicon, 35(4), 1997, pp. 529-535
Citations number
31
Categorie Soggetti
Toxicology,"Pharmacology & Pharmacy
Journal title
ISSN journal
00410101
Volume
35
Issue
4
Year of publication
1997
Pages
529 - 535
Database
ISI
SICI code
0041-0101(1997)35:4<529:PAOTIS>2.0.ZU;2-P
Abstract
Metalloproteinases (haemorrhagic or non-haemorrhagic), disintegrins an d most probably C-type lectin-related proteins are derived by the prot eolysis of a common precursor protein. There is a short interdomain se gment between the metalloproteinase and disintegrin domains which will be released into the venom. To determine whether this region of the m olecule contributes to the biological role of the precursors or the pr oducts derived by the proteolysis of the precursors, we synthesized a peptide based on this short segment and examined its toxicity and biol ogical activity. The synthetic peptide did not show any lethal toxicit y, anticoagulant and antiplatelet effects. However, the peptide appear ed to lower the blood pressure of normotensive rats upon infusion, but did not affect the blood levels of triglyceride, total cholesterol, h igh-density lipoproteins or low-density lipoproteins. The peptide, how ever, failed to exhibit any effect on spontaneously hypertensive rats and hence may not have a potential as an antihypertensive agent. Based on these results, we conclude that this interdomain segment may not c ontribute significantly to the biological activity of precursor protei ns. (C) 1997 Elsevier Science Ltd.