Brigitte Guidetti

Synthetic bolaamphiphilic analogs of galactosylceramide (GalCer) potentially binding to the V3 domain of HIV-1 gp 120: key role of their hydrophobicity

New routes in three or four steps to synthetic bolaamphiphilic analogs of galactosylceramide (GalCer) are presented in this work, using unprotected lactose as the starting sugar. Some of these new anionic compounds obtained in good yields bind to the V3 domain of HIV-1 gp 120 and thus are the base of potential low-cost anti HIV-1 drugs. Moreover, structure-activity relationships show that the hydrophobic moiety of the molecule plays a key role in this activity. Synthese de bolaamphiphiles analogues du galactosylceramide (GalCer) pouvant interagir avec la boucle V3 de la gp 120 du VIH-1: role cle′ de leur hydrophobie. De nouveaux compose′s bolaformes analogues du galactosylce′ramide (GalCer) sont pre′sente′s dans ce travail. Leur synthese en trois ou quatre e′tapes met en jeu le lactose non-prote′ge′ comme sucre de de′part. Certains de ces nouveaux compose′s se lient a la boucle V3 de la gp 120 du VIH-1 et constituent donc une base pour obtenir de nouveaux agents anti VIH a faible cout. En outre, les relations structure-activite′ montrent que la partie hydrophobe de la mole′cule joue un role cle′ dans cette activite′.

Molecular organized systems with fluorinated compounds: from synthesis to biological applications

Abstract This review summarizes previous results obtained in synthesis, physicochemical studies and biological applications of fluorinated or semifluorinated compounds. In these series we prepared olefins from which we studied: • the cycloaddition reaction with cyclopentadiene, and the aggregation properties of the obtained substituted norbornenes; • the amidation reaction in formamide microemulsions; • their ability to provide new formulations for blood substitutes or their applications in vitreous surgery. We also prepared new surfactants having polar heads from lactose and glucose derivatives. An interesting phenomenon of gelification in formamide was observed with surfactants synthesized from gluconolactone.

Synthetic neoglycolipids for biological applications: Correlation between their structures and their interactions with membrane proteins

Synthetic glycolipids are of interest for their biological applications requiring interactions with membrane proteins. Depending on their structures, new series of glycolipids have applications in extraction of membrane proteins or medical applications as mimics of natural ligands of proteins.

Soluble analogs of GalCer and suramin as potential inhibitors of HIV-1 infection: Key role of self-association

Lesions observed in the brain and intestine of HIV-infected individuals may stem from a direct infection of CD4−/GalCer+ cells by the virus within these two organs. HIV-infection of such cells may also facilitate entry of the virus through the intestinal mucosa. Apart from treatment with conventional anti-viral agents, the use of drugs that block interactions between the virus and CD4−/GalCer+ cells represents a promising therapeutic strategy in the fight against AIDS. We present here two families of compounds with such activity, namely soluble analogs of GalCer and a family of suramin analogs. The role of self-association is discussed.