期刊
PEPTIDES
卷 21, 期 4, 页码 503-508出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/S0196-9781(00)00174-1
关键词
spinorphin; tynorphin; DPPIII; enkephalin-degrading enzymes
To find a more effective inhibitor than spinorphin (LVVYPWT), an endogenous factor derived from bovine spinal cord, we synthesized spinorphin analogues and assayed their inhibitory activity toward DPPIII among enkephalin-degrading enzymes. Tynorphin (VVYPW), an N-terminal and C-terminal truncated form of spinorphin, exhibited more potent inhibitory activity and an IC50 value of 0.086 +/- 0.05 mu g/ml (n = 4), whereas structures smaller than four amino acid residues exhibited almost no or less activity, suggesting that a five amino acid structure containing a Tyr-Pro residue is essential for the inhibition. The inhibition of DPPIII by tynorphin was predominantly competitive and the K-i value was found to be 7.50 +/- 1.19 x 10(-8) M on Lineweaver-Burk plotting. The inhibitory activity of tynorphin toward other enkephalin-degrading enzymes such as neutral endopeptidase, aminopeptidase, and angiotensin-converting enzyme was not as high as that toward DPPIII, suggesting that tynorphin is a specific inhibitor of DPPIII. In HPLC analysis, human serum cleaved tynorphin rapidly (38% of control at 2 h and background level at 4 h), but in the presence of leuhisitin, an aminopeptidase inhibitor, tynorphin was maintained at the original level for 24 h. These results indicated that tynorphin had a more effective structure for expression of inhibitory activity toward DPPIII. (C) 2000 Elsevier Science Inc. All rights reserved.
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