Rm. Kini et al., PHARMACOLOGICAL ACTIVITY OF THE INTERDOMAIN SEGMENT BETWEEN METALLOPROTEINASE AND DISINTEGRIN DOMAINS, Toxicon, 35(4), 1997, pp. 529-535
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.