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A rat monoclonal antibody that catalyses the hydrolysis of a nitrophenyl-beta-lactam. 2002
Elizabeth L Ostler, and
Christopher J Dean, and
Nicola Barber, and
Maurizio Valeri, and
Stuart James, and
Marina Resmini, and
Guillaume Boucher, and
Nickolas Romanov, and
Keith Brocklehurst, and
Gerard Gallacher
School of Pharmacy and Biomolecular Sciences, University of Brighton, Cockcroft Building, Moulsecoomb, BN2 4GJ, Brighton, UK.
We report the first example of a monoclonal antibody-catalysed hydrolysis of a beta-lactam where the antibodies were generated by a simple transition-state analogue. A rat monoclonal antibody (1/91c/4d/26) generated by using an acyclic 4-nitrophenylphosphate immunogen catalysed the hydrolysis of corresponding 4-nitrophenyl carbonates but, more importantly, also catalysed the hydrolysis of N-(4-nitrophenyl)-azetidinone at pH 8 with k(cat)=8.7 x 10(-6)s(-1) and K(M)=35 microM. This is the first example of a rat monoclonal catalytic antibody.
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