DNA photocleavage by porphyrin-polyamine conjugates.

Guillaume Garcia (1) , Vincent Sarrazy (1) , Vincent Sol (1) , Caroline Le Morvan (1) , Robert Granet (1) , Sandra Alves (2) , Pierre Krausz (1)

1 LCSN - Laboratoire de Chimie des Substances Naturelles
2 SSFMB - Synthèse, Structure et Fonction de Molécules Bioactives

A series of polyamine-porphyrin conjugates bearing two (cis or trans position) or four units of spermidine or spermine was synthesized. We studied the binding of these cationic porphyrins to calf thymus DNA by the means of UV-vis spectroscopy and we investigated their ability to cleave plasmid DNA in the presence of light. DNA binding and DNA photocleavage abilities were found to depend on structural characteristics as (a) the relative positions of the side chains on the porphyrin ring and (b) the nature of the attached side chains (spermidine or spermine). DNA cleavage was also studied in the presence of a singlet oxygen quencher (NaN(3)) and in the presence of a hydroxyl radical scavenger (mannitol). Singlet oxygen was the major species responsible for the cleavage of DNA previously observed. Collectively, these data show that polyamine-porphyrin conjugates could be promising phototherapeutic agents.

Domaines: Biochimie [q-bio.BM]; Chimie organique

Guillaume Garcia, Vincent Sarrazy, Vincent Sol, Caroline Le Morvan, Robert Granet, et al.. DNA photocleavage by porphyrin-polyamine conjugates.. Bioorganic and Medicinal Chemistry, 2009, 17 (2), pp.767-76. ⟨10.1016/j.bmc.2008.11.047⟩. ⟨hal-00696074⟩