Ostler Elizabeth L, Dean Christopher J, Barber Nicola, Valeri Maurizio, James Stuart, Resmini Marina, Boucher Guillaume, Romanov Nickolas, Brocklehurst Keith, Gallacher Gerard
School of Pharmacy and Biomolecular Sciences, University of Brighton, Cockcroft Building, Moulsecoomb, BN2 4GJ, Brighton, UK.
Biochem Biophys Res Commun. 2002 Nov 29;299(2):273-6. doi: 10.1016/s0006-291x(02)02604-9.
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.