Hirschmann R, Smith A B, Taylor C M, Benkovic P A, Taylor S D, Yager K M, Sprengeler P A, Benkovic S J
Department of Chemistry, University of Pennsylvania, Philadelphia 19104.
Science. 1994 Jul 8;265(5169):234-7. doi: 10.1126/science.8023141.
Monoclonal antibodies, induced with a phosphonate diester hapten, catalyzed the coupling of p-nitrophenyl esters of N-acetyl valine, leucine, and phenylalanine with tryptophan amide to form the corresponding dipeptides. All possible stereoisomeric combinations of the ester and amide substrates were coupled at comparable rates. The antibodies did not catalyze the hydrolysis of the dipeptide product nor hydrolysis or racemization of the activated esters. The yields of the dipeptides ranged from 44 to 94 percent. The antibodies were capable of multiple turnovers at rates that exceeded the rate of spontaneous ester hydrolysis. This achievement suggests routes toward creating a small number of antibody catalysts for polypeptide syntheses.
用膦酸二酯半抗原诱导产生的单克隆抗体，催化了N-乙酰缬氨酸、亮氨酸和苯丙氨酸的对硝基苯酯与色氨酸酰胺的偶联反应，以形成相应的二肽。酯和酰胺底物的所有可能的立体异构组合都以相当的速率进行偶联。这些抗体既不催化二肽产物的水解，也不催化活化酯的水解或消旋化。二肽的产率在44%至94%之间。这些抗体能够以超过自发酯水解速率的速度进行多次周转。这一成果为创建少量用于多肽合成的抗体催化剂指明了方向。
