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

Autori
Pesa, Nela ; Smith, Karen ; Greenman, John ; Boyle, Ross W.

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Journal of Porphyrins and Phthalocyanines / Kadish, Karl M. - Dijon : Society of porphyrins and phthalocyanines, 2004, 558-558

Skup
ICPP-3: Third International Conference on Porphyrins and Phthalocyanines

Mjesto i datum
New Orleans (LA), Sjedinjene Američke Države, 11.07.2004. - 17.07.2004

Vrsta sudjelovanja
Predavanje

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
Photodynamic therapy; Porphyrin; Bioconjugation

Sažetak
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.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Biologija

POVEZANOST RADA