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

Article abstract of DOI:10.1016/0040-4020(96)00197-4

A bifunctional activity label 1c has been constructed for the selection of active β-lactamases displayed on filamentous bacteriophage. It features an original 6-sulfonylamido-penam sulfone moiety, as β-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.