Design and synthesis of a bifunctional label for selection of beta-lactamase displayed on filamentous bacteriophage by catalytic activity

A bifunctional activity label 1c has been constructed for the selection of active beta-lactamases displayed on filamentous bacteriophage. It features an original 6-sulfonylamido-penam sulfone moiety, as beta-lactamase suicide-inhibitor, and a biotinyl residue, for separation by affinity chromatography, connected through a linker including a cleavable disulfide bond. The inhibitor 28 resulted from coupling of methoxymethyl 6-aminopenicillinate 8 with N-protected (aminoethoxy)ethoxyethanesulfonyl chloride 23, followed by oxidation into the corresponding sulfone 25, and usual deprotections. The biotinyl ester 32 reacted with 3-(2-aminoethyldithio)propanoic acid 31 as linker, to give 33 which was further activated as pentafluorophenol ester 34b. Final coupling of the building blocks 28 and 34b gave the target label 1c. Copyright (C) 1996 Elsevier Science Ltd