Angliker H, Wikstrom P, Rauber P, Shaw E
Biochem J. 1987 Feb 1;241(3):871-5. doi: 10.1042/bj2410871.
The synthesis of two lysylfluoromethanes is described by an extension of the synthesis method of Rauber, Angliker, Walker & Shaw [(1986) Biochem. J. 239, 633-640]. Ala-Phe-Lys-CH2F was found to be an active-centre-directed inhibitor of plasmin and trypsin, as is the corresponding chloromethane. However, the rate of covalent-bond formation is about an order of magnitude lower at 25 degrees C for the fluoro derivative. It was, in addition, an extremely effective inactivator of cathepsin B at pH 5.4 and 6.4. The chemical reactivity of fluoromethanes was compared with that of chloromethanes as alkylators of GSH. At pH 7.4 and 37 degrees C, a fluoromethane has 1/500th the reactivity of a chloromethane. A comparison of the rates of reaction of the fluoromethane with cathepsin B and with GSH at pH 6.4 revealed an enhancement of 10(8)-fold for the alkylation of the enzyme, ascribable largely to a proximity effect.
通过扩展劳伯、安利克、沃克和肖的合成方法[（1986年）《生物化学杂志》239卷，633 - 640页]描述了两种赖氨酰氟甲烷的合成。发现丙氨酰 - 苯丙氨酰 - 赖氨酰 - 甲基氟（Ala - Phe - Lys - CH₂F）是纤溶酶和胰蛋白酶的活性中心导向抑制剂，相应的氯甲烷也是如此。然而，在25℃时，氟代衍生物的共价键形成速率比氯代衍生物低约一个数量级。此外，它在pH 5.4和6.4时是组织蛋白酶B的极其有效的失活剂。将氟甲烷与氯甲烷作为谷胱甘肽（GSH）烷基化剂的化学反应性进行了比较。在pH 7.4和37℃时，氟甲烷的反应活性是氯甲烷的1/500。在pH 6.4时，氟甲烷与组织蛋白酶B和与谷胱甘肽的反应速率比较显示，酶烷基化的增强了10⁸倍，这主要归因于邻近效应。
