NEW STRATEGIES FOR THE DESIGN OF CATALYTIC ANTIBODIES

被引:25
作者
JANDA, KD
机构
[1] Department of Molecular Biology and Chemistry, Research Institute of Scripps Clinic, La Jolla, California, 92037
关键词
D O I
10.1021/bp00003a002
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
A new approach is advanced which is aimed at expanding the scope of antibody catalysis. It entails the design and synthesis of haptens that will elicit antibodies to catalyze acyl transfer reactions by a methodology which we term “bait and switch” catalysis. What we have done involves the placement of a point charge on the hapten in close proximity to, or in direct substitution for, a chemical functional group we wish to transform in the respective substrate. The haptenic charge should induce a complementary charge (on an amino acid residue) at the binding site. The substrate will lack this charge but will retain a similar overall structure. The monoclonal antibodies that bind these substrates now have the potential to act as general acids/bases for substrates having hydrolyzable functional groups. Copyright © 1990 American Institute of Chemical Engineers (AIChE)
引用
收藏
页码:178 / 181
页数:4
相关论文
共 17 条
[1]  
Cleland W.W., Statistical Analysis of Enzyme Kinetic Data, Methods in Enzymology, 63, pp. 116-117, (1979)
[2]  
Fersht A., Enzyme Structure and Mechanisms, (1985)
[3]  
Iverson B.L., Lerner R.A., Sequence‐Specific Peptide Cleavage Catalyzed by an Antibody, Science (Washington, D.C.), 241, (1989)
[4]  
Jacobs J., Schultz P.G., Sugasawara R., Powell M., Catalytic Antibodies, J. Am. Chem. Soc., 109, (1987)
[5]  
Janda K.D., Lerner R.A., Tramontano P.J., Antibody Catalysis of Bimolecular Amide Formation, J. Am. Chem. Soc., 110, (1988)
[6]  
Janda K.D., Schloeder D., Benkovic S.J., Lerner R.A., Induction of an Antibody That Catalyzes the Hydrolysis of an Amide Bond, Science (Washington, D.C.), 241, (1988)
[7]  
Janda K.D., Benkovic S.J., Lerner R.A., Catalytic Antibodies with Lipase Activity Including R or S Substrate Selectivity, Science (Washington, D.C.), 244, (1988)
[8]  
Jencks W.P., Catalysis in Chemistry and Enzymology, (1969)
[9]  
Lerner R.A., Benkovic S.J., Principles of Antibody Catalysis, BioEssays, 9, (1988)
[10]  
Pollack S.J., Nakayama G.R., Schultz P.G., Introduction of Nucleophiles and Spectroscopic Probes Into Antibody Combining Sites, Science (Washington, D.C.), 242, (1988)