Design and synthesis of a Mn(III)-porphyrin steroid conjugate used as a new cleavable affinity label: on the road to semi-synthetic catalytic antibodies

We here report the synthesis of a novel porphyrin-steroid conjugate which was designed for the site-specific incorporation of a non-natural heme cofactor at the binding site of an anti-estradiol antibody, in order to get a semi-synthetic catalytic antibody with a monooxygenase-like activity. The general strategy involved a coupling reaction between a testosterone modified by an arm bearing a cleavable disulfide bridge and a meso-tetraarylporphyrin bearing two successive meso-ortho-substituted-phenyl rings, α,α-5,10-bis-[{o-(2-carboxyethyl)carboxamido}phenyl]-15,20-diphenyl-porphyrin. The final porphyrin-steroid conjugate was successfully purified and fully characterized, and was subsequently metalated with manganese acetate. The metalloporphyrin moiety will be used to be coupled with the antibody to generate a new biocatalyst with monooxygenase-like activities.