Méthodologie de synthèse pour l'élaboration de photo-sensibilisateurs sélectifs à visée anti-cancéreuse

Le développement d'anti-cancéreux efficaces passe par la mise au point de molécules à toxicité contrôlée qui s'accumuleraient spécifiquement au niveau des zones tumorales. Dans ce but nous avons conçu deux photosensibilisateurs hybrides originaux, composés d'un peptide inhibiteur de la neoangiogenèse tumorale et de mesoporphyrines, fixés aux extrémités d'une chaîne tétraéthylène glycol. Pour cela, les méthodes de couplage peptidique et la cyclo-addition de Click-Chemistry ont été mises en œuvre. Dans un second temps, nous avons développé une méthode originale conduisant, en phase solide, à la désymétrisation de la protoporphyrine IX. Cette approche donne les dérivés aminés sous forme protégée (NHFmoc) qui représentent une nouvelle classe de porphyrines bi-fonctionnelles, permettant la construction d'oligomères photosensibilisateurs et l'inclusion de chromophores dans les séquences de synthèses peptidiques en phase solide. Tous les composés obtenus ont été caractérisés.LIMOGES-BU Sciences (870852109) / SudocSudocFranceF

Bio-inspired cationic polymerization of isoprene and analogues: state-of-the-art

Natural rubber (NR), which is polyisoprene about 100% 1,4-cis of high molar mass, > 10(6) g mol(-1), is mainly produced in southeast Asia and represents around 40%-45% of total worldwide elastomer consumption. Whereas more than 2500 plant species are able to produce polyisoprenoids, the only established commercial source of NR is Hevea braziliensis. NR presents high performance properties that are so far not matched by synthetic rubbers. As a consequence, NR is irreplaceable in many applications (aircraft tires, surgery gloves etc.). Nature and synthetic polymer chemists start from different substrates to synthesize polyisoprenes, i.e. isopentenyl pyrophosphate (IPP), which is a universal building brick utilized by plants and animals, and isoprene monomer, respectively. Nevertheless, we proposed that the elementary processes involved in the biosynthesis of NR are very similar to those of cationic polymerization. In the course of a study on bio-inspired cationic polymerization of isoprene and IPP analogues, it appeared that cationic polymerization of isoprene proceeds readily and leads mainly to its 1,4-trans addition; such a process nevertheless remains difficult to control due to the occurrence of many side reactions (transfer, protic initiation, branching, cyclization). The present paper describes our understanding of the cationic polymerization of isoprene and its analogues catalyzed by different Lewis acids, in solution and aqueous dispersions

HbIDI, SlIDI and EcIDI: A comparative study of isopentenyl diphosphate isomerase activity and structure

In this study, we cloned, expressed and purified the isopentenyl diphosphate isomerases (IDIs) from two plants, Hevea brasiliensis and Solanum lycopersicum, and compared them to the already well characterized Escherichia coli IDI. Phylogenetic analysis showed high homology between the three enzymes. Their catalytic activity was investigated in vitro with recombinant purified enzymes and in vivo by complementation colorimetric tests. The three enzymes displayed consistent activities both in vitro and in vivo. In term of structure, studied by ATR-FTIR and molecular modeling, it is clear that both plant enzymes are more related to their human homologue than to E. coli IDI. But it is assumed that EcIDI represent the minimalistic part of the catalytic core, as both plant enzymes present a supplementary sequence forming an extra alpha-helice surrounding the catalytic site that could facilitate the biocatalysis. New potential biotechnological applications may be envisaged. (C) 2016 Elsevier B.V. and Societe Francaise de Biochimie et Biologie Moleculaire (SFBBM). All rights reserved