Department of Chemistry, Yale University, New Haven, Connecticut 06520-8107, United States.
J Am Chem Soc. 2012 Dec 5;134(48):19501-3. doi: 10.1021/ja3092642. Epub 2012 Nov 19.
X-ray crystal structures at 2.9 Å resolution are reported for two complexes of catechol diethers with HIV-1 reverse transcriptase. The results help elucidate the structural origins of the extreme antiviral activity of the compounds. The possibility of halogen bonding between the inhibitors and Pro95 is addressed. Structural analysis reveals key interactions with conserved residues P95 and W229 of importance for design of inhibitors with high potency and favorable resistance profiles.
报道了两种儿茶酚二醚与 HIV-1 逆转录酶复合物的 2.9Å 分辨率的 X 射线晶体结构。研究结果有助于阐明这些化合物具有极强抗病毒活性的结构起源。探讨了抑制剂与 Pro95 之间可能存在的卤素键合。结构分析揭示了与保守残基 P95 和 W229 的关键相互作用,对于设计具有高效力和有利耐药性的抑制剂非常重要。