Williams, C H and Yamamoto, T and Walsh, D M and Allsop, D (1993) Endopeptidase 18.104.22.168 converts N-1-(R,S)carboxy-3-phenylpropyl-Ala-Ala-Phe-p-carboxyanilide into a potent inhibitor of angiotensin-converting enzyme. Biochemical Journal, 294 (3). pp. 681-684. ISSN 0264-6021Full text not available from this repository.
It was reported recently that N-1-(R,S)carboxy-3-phenylpropyl-Ala-Ala-Phe-p-carboxyanilide (CPP-A-A-F-pAB), an inhibitor of endopeptidase 22.214.171.124 (E-24.15), also inhibits angiotensin-converting enzyme (ACE) from rabbit lung. We have found that this compound is without effect on ACE purified from pig kidney, at a concentration some 1000-fold greater than the Ki reported for inhibition of the enzyme from lung. However, preincubation of CPP-A-A-F-pAB with neutral endopeptidase 126.96.36.199 (E-24.11) does result in potent inhibitory effects on ACE. We have shown this to be due to formation of a fragment, CPP-A-A, the structure of which is closely related to ACE inhibitors such as enalaprilat. CPP-A-A was found to be a potent inhibitor of pig ACE. Under the conditions used it had an IC50 value of 1.6 x 10(-8) M, compared with the value obtained for captopril of 7.5 x 10(-10) M. These results have important implications for studies of E-24.15 when using CPP-A-A-F-pAB in vivo or in crude tissue extracts where E-24.11 might also be present.
|Journal or Publication Title:||Biochemical Journal|
|Uncontrolled Keywords:||Amino Acid Sequence ; Angiotensin-Converting Enzyme Inhibitors ; Animals ; Chromatography, High Pressure Liquid ; Kidney ; Metalloendopeptidases ; Molecular Sequence Data ; Neprilysin ; Oligopeptides ; Rabbits ; Swine|
|Departments:||Faculty of Health and Medicine > Biomedical & Life Sciences|
|Deposited On:||07 Nov 2011 17:01|
|Last Modified:||18 Jan 2016 01:06|
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