- Toward bifunctional antibody catalysis
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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 >105-fold rate acceleration over background and an effective molarity of >104 M for its catalytic base. These properties compare favorably to the efficiencies achieved by the best previously characterized antibodies with substantially more reactive substrates.
- Kikuchi, Kazuya,Hannak, Renate B.,Guo, Mao-Jun,Kirby, Anthony J.,Hilvert, Donald
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p. 6189 - 6196
(2007/10/03)
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- PIPERIDINE/CYCLOHEXANE CARBOXAMIDE DERIVATIVES FOR USE AS VANILLOID RECEPTOR MODULATORS
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Certain compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein R1, R2, P, P', X, m and n are as defined in the specification, a process for preparing such compounds, a pharmaceutical composition c
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Page/Page column 13
(2010/02/10)
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