Synthetic Bivalent CD4-Mimetic Miniproteins Show Enhanced Anti-HIV Activity over the Monovalent Miniprotein

详细信息    查看全文

• 作者：Hengguang Li ; Haijing Song ; Alonso Heredia ; Nhut Le ; Robert Redfield ; George K. Lewis ; and Lai-Xi Wang
• 刊名：Bioconjugate Chemistry
• 出版年：2004
• 出版时间：July 2004
• 年：2004
• 卷：15
• 期：4
• 页码：783 - 789
• 全文大小：126K
• 年卷期：v.15,no.4(July 2004)
• ISSN：1520-4812

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.