PubMed · 9206829
The source did not provide an abstract. Follow the original record for more information.
Explore connections, maps & timelines
G F Joyce. 1997-06-13. Evolutionary chemistry: getting there from here.. https://doi.org/10.1126/science.276.5319.1658
Cite the original work for its findings. Save a collection to share your selection of sources.
KEEP EXPLORING
Explore the source record for details and available documents.
Antibodies that catalyze the deprotonation of unactivated benzisoxazoles to give the corresponding salicylonitriles were prepared using as antigen a 2-aminobenzimidazolium derivative coupled to a carrier protein via its benzene ring. The hapten was designed to induce an antibody binding site with both a base and an acid, in position to initiate proton transfer and stabilize developing negative charge at the phenoxide leaving group, respectively. Consistent with this design, the catalysts exhibit bell-shaped pH-rate profiles, while chemical modification identified several functional groups that could participate in bifunctional catalysis. One of the antibodies, 13G5, is particularly notable in catalyzing the elimination of 6-glutaramidebenzisoxazole with a > 10(5)-fold rate acceleration over background and an effective molarity of > 10(4) M for its catalytic base. These properties compare favorably to the efficiencies achieved by the best previously characterized antibodies with substantially more reactive substrates.
Abzymes (catalytic autoantibodies) belong to an absolutely new group of physiologically active substances with dual characteristics: they represent a pool of canonical autoantibodies and possess catalytic activity. Among them, proteolytic and DNA-hydrolyzing autoantibodies are of special value. Abzymes are an important pathogenic factor in the progression of clinical autoimmunity syndrome. The presence of autoantibodies against various autoantigens is accompanied by their high catalytic potential. The increase in this activity correlates with serum levels of the autoantibodies, clinical manifestations of autoimmune disorders, disease severity and the rate of progressing disability. Abzymes are crucial for immune homeostasis regulation. They can be of practical value in the development of modern immunodiagnostic tools and schedules of immunotherapy.