title: Synthesis of new covalently bound kappa-carrageenan-AZT conjugates with improved anti-HIV activities.
abstract: This paper describes the first covalent synthesis of kappa-carrageenan-3'-azido-3'-deoxythymidine (AZT) conjugates. A succinate diester spacer was used to covalently couple AZT onto kappa-carrageenan, resulting in a tripartite prodrug. Two methods (UV and radioactive counting) are described and validated to determine the AZT loading onto the kappa-carrageenan carrier. This polymeric carrier, through its own intrinsic anti-HIV activity, is expected to act not only as a drug delivery agent but also as an anti-HIV agent. Synergism between the two drugs (kappa-carrageenan and AZT) was demonstrated when MT-4 cells were preincubated with the kappa-carrageenan-AZT conjugate prior to HIV-1-infection. A threshold of AZT loaded onto the kappa-carrageenan was required to achieve this synergistic effect. Such kappa-carrageenan-AZT conjugates could be of great therapeutic interest because these conjugates, which contain a low AZT concentration, present improved anti-HIV activities relative to free AZT. Moreover, kappa-carrageenan is a well-tolerated biopolymer, already used in the food industry.
authors.affiliation: Laboratoire de Chimie Biomoléculaire, Faculté des Sciences de Luminy, 163 avenue de Luminy, case 901, 13288 Marseille Cedex 9, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Vlieghe
authors.forename: Thierry
authors.initials: T
authors.lastname: Clerc
authors.forename: Christophe
authors.initials: C
authors.lastname: Pannecouque
authors.forename: Myriam
authors.initials: M
authors.lastname: Witvrouw
authors.forename: Erik
authors.initials: E
authors.lastname: De Clercq
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Salles
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Kraus
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002240:Carbohydrate Sequence; D002351:Carrageenan / Q000138:chemical synthesis / Q000737:chemistry*; D002478:Cells, Cultured; D004357:Drug Synergism; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008969:Molecular Sequence Data; D011355:Prodrugs / Q000138:chemical synthesis* / Q000494:pharmacology; D015215:Zidovudine / Q000138:chemical synthesis / Q000737:chemistry*
chemical_list: D019380:Anti-HIV Agents; D011355:Prodrugs; D015215:Zidovudine; D002351:Carrageenan