抑制和灭活胆碱乙酰转移酶的氧化还原反应试剂。

Redox reactive reagents inhibiting and inactivating choline acetyltransferase.

作者信息

Patel P J, Wohlfeil E R, Stahl S S, McLaughlin K A, Hudson R A

机构信息

Department of Medicinal and Biological Chemistry, College of Pharmacy, University of Toledo, OH 43606.

出版信息

Biochem Biophys Res Commun. 1991 Mar 15;175(2):407-13. doi: 10.1016/0006-291x(91)91579-2.

DOI:10.1016/0006-291x(91)91579-2

PMID:2018491

Abstract

3-Trimethylammoniomethyl catechol and N,N-dimethylepinephrine (catecholine) are redox reactive reagents which possess quaternary ammonium functional groups and the capacity to inhibit or inactivate choline binding macromolecules which mediate cholinergic neuronal function. Earlier studies reported the synthesis of 3-trimethylammoniomethyl catechol and demonstrated its redox-dependent covalent inactivation of the nicotinic acetylcholine receptor (Nickoloff et al., Biochemistry 24, 999-1007 (1985)]. Here we present the synthesis of catecholine and show that both 3-trimethylammoniomethyl catechol and catecholine are weak noncompetitive inhibitors (Ki = 15 +/- 6 and 25 +/- 4 mM, respectively) of choline acetyltransferase (EC 2.3.1.6). Both agents irreversibly inactivate the enzyme.

摘要

3 - 三甲基铵甲基儿茶酚和N，N - 二甲基肾上腺素（儿茶胆碱）是具有氧化还原反应性的试剂，它们含有季铵官能团，并且能够抑制或使介导胆碱能神经元功能的胆碱结合大分子失活。早期研究报道了3 - 三甲基铵甲基儿茶酚的合成，并证明了其对烟碱型乙酰胆碱受体的氧化还原依赖性共价失活作用（Nickoloff等人，《生物化学》24，999 - 1007（1985））。在此，我们展示了儿茶胆碱的合成，并表明3 - 三甲基铵甲基儿茶酚和儿茶胆碱都是胆碱乙酰转移酶（EC 2.3.1.6）的弱非竞争性抑制剂（Ki分别为15±6和25±4 mM）。这两种试剂均可使该酶不可逆地失活。