[Synthetic peptide as retinoid vector and antiproliferative agent]

First part: Structure, conformational behaviour and vectorization properties of a peptide (PFNLS) designed by association of a fusion peptide and a nuclear localization sequence is described. Tryptophan fluorescence quenching measurements show that ten peptide molecules bind one all trans retinol or all trans retinoic acid molecule with a strong affinity (Kd' = 40 nM). And is able to help the internalization of all-trans retinol in human fibroblasts. Stoichiometry, structure and affinity of the binding can be compared with those of cellular retinoid binding proteins (CRBP), the structure of which is an antiparallel beta barrel. Second part: Cytotoxic properties of the amphiphilic synthetic peptide are presented. Comparative analysis of proliferating, differentiated and confluent H9C2 adherent cells shows a correlation between toxicity and cell cycle stage (proliferating cells). Electrophysiological measurements on Xenopus laevi oocytes bathed in the peptide also demonstrate the induction of cationic currents, which are voltage dependent. These results allow us to hypothesize that the observed toxicity is related to membrane hyperpolarization of proliferating cells at the G1/S cell cycle phase transition. An important point is that in the case of the "peptide-retinoid" complex, no cytotoxicity is observed.