α,α-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-α,α-trehalose was obtained from selective bromination of, α,α-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 α,α-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.