文摘
HIV-1 envelope glycoprotein gp120 is displayed as a trimeric complex on the surface of virion andinfected T-cells, making it a typical multivalent target. This paper describes the design and synthesisof bivalent CD4-mimetic miniproteins to target the conserved CD4-binding pockets in the trimericgp120. Using miniprotein CD4M9 as the model inhibitor, we created bivalent inhibitors in which twoCD4M9 moieties were tethered by a spacer of varied length and evaluated their anti-HIV activityusing a cell culture assay. The synthetic bivalent miniproteins showed 5-21-fold enhancement inanti-HIV activity over the monovalent miniprotein. The activity enhancement is dependent on thelength of the spacer. The study suggests that targeting the oligomeric gp120 complex by novelmultivalent ligands offers a valuable strategy for developing highly specific and effective HIV entryinhibitors.