Enhanced potency of bivalent small molecule gp41 inhibitors

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• 作者：Vladimir Sofiyev^a ; Hardeep Kaur^a ; Beth A. Snyder^c ; Priscilla A. Hogan^c ; Roger G. Ptak^c ; Peter Hwang^d ; Miriam Gochin^a ; ^b ; ^{miriam.gochin@tu.edu}
• 关键词：HIV-1 gp41 ; Hydrophobic pocket ; Fusion inhibition ; Peptidomimetic inhibitors ; Bivalent inhibitors ; Fluorescence ; Surface plasmon resonance ; Kinetics ; Cooperativity
• 刊名：Bioorganic & Medicinal Chemistry
• 出版年：2017
• 出版时间：1 January 2017
• 年：2017
• 卷：25
• 期：1
• 页码：408-420
• 全文大小：2646 K
• 卷排序：25

文摘

Bivalent gp41 inhibitors were 40–60-fold more potent than monomers. Binding potency was not significantly improved by dimerization. Potency was correlated to slower off-rates. Data could be explained by a bidentate binding model for the dimers. The kinetic dependence may be due to transience of the targeted intermediate.