title: Anti-HIV activities of precisely defined, semirigid, carboxylated alternating copolymers.
abstract: Di-tert-butyl (E)-4,4'-stilbenedicarboxylate and tert-butyl 4-vinylbenzoate were copolymerized with maleic anhydride and tert-butyl 4-maleimidobenzoate, individually and respectively. After conversion into polyanions, these four copolymers exhibited activity against four HIV-1 strains: IIIb, BaL, JR-CSF, and 92UG037. For both the IIIb and BaL HIV-1 strains, the lowest IC50 (0.095 and 0.23 μg/mL, respectively) values were obtained with poly(4,4'-stilbenedicarboxylate-alt-maleic acid) (DCSti-alt-MA). For JR-CSF and 92UG037, both tier 2 clinical isolates but different clades, DCSti-alt-MA exhibited the lowest IC50 (0.76 and 0.75 μg/mL, respectively). Although DCSti-alt-MA had the lowest IC50 in μg/mL for each strain, the other copolymers had IC50s less than 2-fold higher. Further, these copolymers achieved high selectivity indices (>100) for these clinical isolates. Polymer rigidity, as measured by the statistical segment length, emerged as a key property when comparing anti-HIV activities with those of other polyanions. A speculative illustration was proposed for possible modes of inhibition.
authors.affiliation: Department of Chemistry MC0212 and Macromolecules and Interfaces Institute MC0344, Virginia Tech , Blacksburg, Virginia 24061, United States.
authors.forename: Alice M
authors.initials: AM
authors.lastname: Savage
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.forename: Lindsay E
authors.initials: LE
authors.lastname: Matolyak
authors.forename: Gustavo F
authors.initials: GF
authors.lastname: Doncel
authors.forename: S Richard
authors.initials: SR
authors.lastname: Turner
authors.forename: Richard D
authors.initials: RD
authors.lastname: Gandour
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects* / Q000302:isolation & purification; D006367:HeLa Cells; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000821:virology; D008299:Maleic Anhydrides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D008301:Maleimides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D058105:Polymerization; D011145:Polyvinyls / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013045:Species Specificity; D013329:Structure-Activity Relationship
chemical_list: D019380:Anti-HIV Agents; D008299:Maleic Anhydrides; D008301:Maleimides; D011145:Polyvinyls; C000594983:poly((di-tert-butyl 4,4'-stilbenedicarboxylate)-alt-(tert-butyl 4-maleimidobenzoate); C000594981:poly((di-tert-butyl 4,4'-stilbenedicarboxylate)-alt-maleic anhydride); C000594984:poly((tert-butyl 4-vinylbenzoate)-alt-(tert-butyl 4-maleimidobenzoate)); C000594982:poly((tert-butyl 4-vinylbenzoate)-alt-maleic anhydride)