Chen W S, Bohlken D P, Plapp B V
J Med Chem. 1981 Feb;24(2):190-3. doi: 10.1021/jm00134a012.
Active-site-directed reagents, of the general structure omega-(BrCH2CONH)RCOY, where R = alkyl, aryl, or aralkyl, and Y = OH or NH2, inactivated horse, mouse, rat, and human liver alcohol dehydrogenases at widely different rates, reflecting differences in reagent specificity and in the structures of the enzymes. Treatment of mice and rats with either of two optimally specific reagents, p-(XCH2CONH)C6H4(CH2)3CONH2, where X = Br (7) or CH3SO3 (10), partially (20 to 40%) inactivated alcohol dehydrogenase in liver, inhibited ethanol metabolism, and prolonged the impairment of coordination produced by ethanol in these animals. Although the dose of 7 used (0.13 mmol/kg) approximated the LD50, 10 was effective at a dose of 0.48 mmol/kg that was not acutely toxic.
具有通式ω-(BrCH2CONH)RCOY的活性位点导向试剂，其中R = 烷基、芳基或芳烷基，Y = OH或NH2，能以差异很大的速率使马、小鼠、大鼠和人肝脏乙醇脱氢酶失活，这反映了试剂特异性和酶结构上的差异。用两种最佳特异性试剂中的任何一种，即p-(XCH2CONH)C6H4(CH2)3CONH2（其中X = Br (7) 或CH3SO3 (10)）处理小鼠和大鼠，可使肝脏中的乙醇脱氢酶部分（20%至40%）失活，抑制乙醇代谢，并延长乙醇在这些动物中产生的协调功能损害。尽管所用的7的剂量（0.13 mmol/kg）接近半数致死量，但10在剂量为0.48 mmol/kg时有效，且无急性毒性。
