title: Alpha,alpha-trehalose derivatives bearing guanidino groups as inhibitors to HIV-1 Tat-TAR RNA interaction in human cells.
abstract: Replication of HIV-1 requires specific interactions of Tat protein with TAR RNA. Disruption of Tat-TAR RNA interaction could inhibit HIV-1 replication. Here four target compounds were designed and synthesized to bind to TAR RNA for blocking the interaction of Tat-TAR RNA. The core molecule 6,6'-diamino-6,6'-dideoxy-alpha,alpha-trehalose was obtained from selective bromination of, alpha,alpha-trehalose at C-6,6', followed by acetylation, azide displacement, deacetylation, and reduction. Coupling of the core molecule with the protected amino acid, then deprotection and guanidinylation generated the novel alpha,alpha-trehalose derivatives. Their abilities to inhibit Tat-TAR RNA interaction in human cells were determined by a Tat-dependent HIV-1 LTR-driven CAT assays.
authors.affiliation: National Research Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100083, PR China.
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.forename: Zhidong
authors.initials: Z
authors.lastname: Xu
authors.forename: Pengfei
authors.initials: P
authors.lastname: Tu
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Yu
authors.forename: Sulong
authors.initials: S
authors.lastname: Xiao
authors.forename: Ming
authors.initials: M
authors.lastname: Yang
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001667:Binding, Competitive; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase; D015696:Gene Products, tat / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019791:Guanidine / Q000737:chemistry; D016325:HIV Long Terminal Repeat / Q000187:drug effects*; D015497:HIV-1; D006801:Humans; D012367:RNA, Viral / Q000037:antagonists & inhibitors / Q000378:metabolism; D013329:Structure-Activity Relationship; D014199:Trehalose / Q000138:chemical synthesis / Q000494:pharmacology*; D054322:tat Gene Products, Human Immunodeficiency Virus
chemical_list: D019380:Anti-HIV Agents; D015696:Gene Products, tat; D012367:RNA, Viral; D054322:tat Gene Products, Human Immunodeficiency Virus; D014199:Trehalose; D015500:Chloramphenicol O-Acetyltransferase; D019791:Guanidine