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Catalytic Antibodies: A New Class of Transition‐State Analogues Used to Elicit Hydrolytic Antibodies
Author(s) -
Shokat Kevan M.,
Ko Marcia K.,
Scanlan Thomas S.,
Kochersperger Lynn,
Yonkovich Shirlee,
Thaisrivongs Suvit,
Schultz Peter G.
Publication year - 1990
Publication title -
angewandte chemie international edition in english
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 0570-0833
DOI - 10.1002/anie.199012961
Subject(s) - chemistry , catalysis , metalation , combinatorial chemistry , enzyme catalysis , hydrolysis , transition state analog , organic chemistry , active site
The design and generation of selective catalysts is an important aim of chemists and biologists. A number of successful strategies have emerged, including the synthesis and derivatization of synthetic hosts, the chemical modification and site‐directed mutagenesis of enzymes, and the attenuation of natural enzyme activities in organic solvents. Since 1986 several laboratories have exploited the immune system to generate selective catalysts capable of catalyzing a wide range of chemical transformations. These include acyl transfer, β‐elimination, carbon—carbon bond‐forming, carbon—carbon bond‐cleaving, porphyrin metalation, peroxidation, and redox reactions. The variety and number of transformations catalyzed by antibodies in this short period of time is testament to the versatility and power of the method in generating selective catalysts for applications in chemistry, biology, and medicine. Here we report the use of a new class of uncharged transition‐state analogues for generating antibodies capable of catalyzing ester and carbonate hydrolysis. These antibodies are compared to those raised against tetrahedral phosphate and phosphonate transition‐state analogues.