Deng Shi-Xian, Bharat Narine, Fischman Marian C, Landry Donald W
Department of Medicine, Division of Clinical Pharmacology and Experimental Therapeutics, Columbia University, College of Physicians and Surgeons, 630 West 168th Street, New York, NY 10032, USA.
Proc Natl Acad Sci U S A. 2002 Mar 19;99(6):3412-6. doi: 10.1073/pnas.042700599. Epub 2002 Mar 12.
Cocaine covalently modifies proteins through a reaction in which the methyl ester of cocaine acylates the epsilon-amino group of lysine residues. This reaction is highly specific in vitro, because no other amino acid reacts with cocaine, and only cocaine's methyl ester reacts with the lysine side chain. Covalently modified proteins were present in the plasma of rats and human subjects chronically exposed to cocaine. Modified endogenous proteins are immunogenic, and specific antibodies were elicited in mouse and detected in the plasma of human subjects. Covalent modification of proteins could explain cocaine's autoimmune effects and provide a new biochemical approach to cocaine's long-term actions.
可卡因通过一种反应共价修饰蛋白质,在该反应中可卡因的甲酯酰化赖氨酸残基的ε-氨基。此反应在体外具有高度特异性,因为没有其他氨基酸与可卡因反应,且只有可卡因的甲酯与赖氨酸侧链反应。长期接触可卡因的大鼠和人类受试者血浆中存在共价修饰的蛋白质。修饰的内源性蛋白质具有免疫原性,可在小鼠体内引发特异性抗体,并在人类受试者血浆中检测到。蛋白质的共价修饰可以解释可卡因的自身免疫作用,并为可卡因的长期作用提供一种新的生化方法。