engleski

Synthesis of Cationic Isothiocyanato Diphenyl Porphyrins, and Their Bioconjugation for Targeted Photodynamic Therapy

It has been found that the synthesis of porphyrins bearing a single isothiocyanato group enables their bioconjugation to monoclonal antibodies (Mabs) under mild conditions, making them suitable photosensitisers for targeted photodynamic therapy. Previously we have highlighted the problem of non-covalent binding of these porphyrins to proteins, which makes targeting less specific. The lowest level of non-covalent binding (less than 5%) was achieved with tetraphenylporphyrin (TPP) possesing charged pyridyl moieties. Unfortunately, TPP's are difficult to convert to the more optically desirable chlorin and bacteriochlorin analogues via osmium tetroxide hydroxylation, a method that works much better with diphenylporphyrins (DPP's). Thus, we decided to synthesise new photosensitisers based on the diphenylporphyrin structure bearing a single isothiocyanate group for bioconjugation. Our main aim was to optimise solubility, minimise non-covalent binding to proteins, and improve photodynamic properties by converting DPP's into their bacteriochlorin analogues. We prepared the DPP analogue of the previously reported tripyridiniumyl TPP and, using a similar synthetic route, two other DPP's with quaternised nitrogen in their structure. Such structures proved to be hydrophilic and sufficiently soluble in aqueous conditions required for bioconjugation to proteins. The routes leading to these compounds and their conjugation to a number of Mabs will be described. Biodata realting to specificity and photoactivity will also be presented for all porphyrin-Mab conjugates.

Photodynamic therapy; Porphyrin; Bioconjugation

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