PEPTIDE-SYNTHESIS CATALYZED BY AN ANTIBODY CONTAINING A BINDING-SITE FOR VARIABLE AMINO-ACIDS
PEPTIDE-SYNTHESIS CATALYZED BY AN ANTIBODY CONTAINING A BINDING-SITE FOR VARIABLE AMINO-ACIDS
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DOI：
10.1126/science.8023141
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发表时间：
1994-07-08
期刊：
影响因子：
56.9
通讯作者：
BENKOVIC, SJ
中科院分区：
文献类型：
--
作者：
HIRSCHMANN, R;SMITH, AB;BENKOVIC, SJ
单克隆抗体，诱导与膦酸二酯半抗原，催化N-乙酰基缬氨酸，亮氨酸和苯丙氨酸的对硝基苯基酯与色氨酸酰胺的偶联，形成相应的二肽。酯和酰胺底物的所有可能的立体异构体组合以可比的速率偶联。抗体不催化二肽产物的水解，也不催化活化酯的水解或外消旋化。二肽的产率在44%至94%之间。抗体能够以超过自发酯水解速率的速率进行多次周转。这一成就表明了为多肽合成创造少量抗体催化剂的途径。
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.