期刊
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
卷 12, 期 17, 页码 2349-2353出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/S0960-894X(02)00393-1
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Liquid chromatography electrospray ionization mass spectrometry (LC/ESI-MS) to probe the nature of the covalent E I complex was successfully applied to clarify the mechanism of human sputum elastase (HSE) inhibition by a new inhibitor, ONO-5046. The mass spectrum of the four HSE isozymes displayed their molecular ion peaks at m/z = 26,018, 25,929, 25,200, and 25,054, respectively. Immediately after incubation, inactivation of HSE with ONO-5046 increased the four molecular ion peaks by approximately 84 amu, which was assigned to the mass unit of the pivaloyl moiety of ONO-5046. An additional minute of incubation of E-I complex restored the original molecular ion peaks. These observations strongly suggested that ONO-5046 inactivates HSE by a reversible 'acylation-deacylation' mechanism. (C) 2002 Elsevier Science Ltd. All rights reserved.
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