SUBSTRATE ATTENUATION - AN APPROACH TO IMPROVE ANTIBODY CATALYSIS

被引:30
作者
JANDA, KD
BENKOVIC, SJ
MCLEOD, DA
SCHLOEDER, DM
LERNER, RA
机构
[1] Scripps Res Inst, RES INST, DEPT CHEM, LA JOLLA, CA 92037 USA
[2] PENN STATE UNIV, DEPT CHEM, UNIVERSITY PK, PA 16802 USA
关键词
D O I
10.1016/S0040-4020(01)81784-1
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
Antibodies raised to quinaldine phosphonamide 1a showed no ability to hydrolyze its most homologous substrates amide and ester 2 and 3, respectively. However, within this same set of antibodies some thirteen showed a great propensity to hydrolyse a structurally similar naphthyl ester In addition to heteroatom discrimination one of the antibodies examined in detail displayed an increase in catalytic efficiency presumably via weak apparent binding (k(m)) when phenylesters were employed as substrates. These findings suggest abzyme catalysis may be improved via substrate attenuation.
引用
收藏
页码:2503 / 2506
页数:4
相关论文
共 17 条
[1]   CATALYSIS OF A STEREOSPECIFIC BIMOLECULAR AMIDE SYNTHESIS BY AN ANTIBODY [J].
BENKOVIC, SJ ;
NAPPER, AD ;
LERNER, RA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1988, 85 (15) :5355-5358
[2]  
Benkovic SJ., 1990, CHEMTRACTS ORG CHEM, V3, P1
[3]  
ENGALL E, 1990, METHOD ENZYMOL, V70, P419
[4]   CATALYTIC ANTIBODIES WITH LIPASE ACTIVITY AND R-SUBSTRATE OR S-SUBSTRATE SELECTIVITY [J].
JANDA, KD ;
BENKOVIC, SJ ;
LERNER, RA .
SCIENCE, 1989, 244 (4903) :437-440
[5]   INDUCTION OF AN ANTIBODY THAT CATALYZES THE HYDROLYSIS OF AN AMIDE BOND [J].
JANDA, KD ;
SCHLOEDER, D ;
BENKOVIC, SJ ;
LERNER, RA .
SCIENCE, 1988, 241 (4870) :1188-1191
[6]   ANTIBODY CATALYSIS OF BIMOLECULAR AMIDE FORMATION [J].
JANDA, KD ;
LERNER, RA ;
TRAMONTANO, A .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1988, 110 (14) :4835-4837
[7]  
JANDA KD, 1990, J AM CHEM SOC, V112, P1224
[8]  
JENCKS WP, 1975, ADV ENZYMOL RAMB, V43, P219
[9]   CONTINUOUS CULTURES OF FUSED CELLS SECRETING ANTIBODY OF PREDEFINED SPECIFICITY [J].
KOHLER, G ;
MILSTEIN, C .
NATURE, 1975, 256 (5517) :495-497
[10]   A STEREOSPECIFIC CYCLIZATION CATALYZED BY AN ANTIBODY [J].
NAPPER, AD ;
BENKOVIC, SJ ;
TRAMONTANO, A ;
LERNER, RA .
SCIENCE, 1987, 237 (4818) :1041-1043