Bensel N, Reymond M T, Reymond J L
Departement für Chemie und Biochemie, Universität Bern, Switzerland.
Chemistry. 2001 Nov 5;7(21):4604-12. doi: 10.1002/1521-3765(20011105)7:21<4604::aid-chem4604>3.0.co;2-z.
Screening of monoclonal-antibody libraries generated against the tert-butyl phosphonate hapten 2 and the chloromethyl phosphonate hapten 3 with pivaloyloxymethyl-umbelliferone 1 as a fluorogenic substrate led to the isolation of eleven catalytic antibodies with rate accelerations around kcat/ kuncat = 10(3). The antibodies are not inhibited by the product and accept different acyloxymethyl derivatives of acidic phenols as substrates. The highest activity was found for the bulky, chemically less-reactive pivaloyloxymethyl group: there is no activity with acetoxymethyl or acetyl esters. This difference might reflect the preference of the immune system for hydrophobic interactions in binding and catalysis. Pivalase catalytic antibodies might be useful for activating orally available pivaloyloxymethyl prodrugs.
以新戊酰氧基甲基伞形酮1作为荧光底物，筛选针对叔丁基膦酸酯半抗原2和氯甲基膦酸酯半抗原3产生的单克隆抗体文库，得到了11种催化抗体，其催化速率加速约为kcat/kuncat = 10(3)。这些抗体不受产物抑制，并且接受酸性酚类的不同酰氧基甲基衍生物作为底物。发现体积大、化学活性较低的新戊酰氧基甲基基团具有最高活性：乙酰氧基甲基或乙酰酯没有活性。这种差异可能反映了免疫系统在结合和催化中对疏水相互作用的偏好。新戊酰酶催化抗体可能有助于激活口服可用的新戊酰氧基甲基前药。
