Tamamura H, Sugioka M, Odagaki Y, Omagari A, Kan Y, Oishi S, Nakashima H, Yamamoto N, Peiper S C, Hamanaka N, Otaka A, Fujii N
Graduate School of Pharmaceutical Sciences, Kyoto University, Japan.
Bioorg Med Chem Lett. 2001 Feb 12;11(3):359-62. doi: 10.1016/s0960-894x(00)00664-8.
We report the solution structure of T140, a truncated polyphemusin peptide analogue that efficiently inhibits infection of target cells by T-cell line-tropic strains of HIV-1 through its specific binding to a chemokine receptor, CXCR4. Nuclear magnetic resonance analysis and molecular dynamic calculations revealed that T140 has a rigidly structured conformation constituted by an antiparallel beta-sheet and a type II' beta-turn. A protuberance is formed on one side of the beta-sheet by the side-chain functional groups of the three amino acid residues (L-3-(2-naphthyl)alanine, Tyr5 and Arg14), each of which is indispensable for strong anti-HIV activity. These findings provide a rationale to dissect the structural basis for the ability of this compound to block the interaction between CXCR4 and envelope glycoproteins from T-tropic strains of HIV-1.
我们报道了T140的溶液结构，T140是一种截短的海葵抗菌肽类似物，它通过与趋化因子受体CXCR4特异性结合，有效抑制T细胞系嗜性的HIV-1毒株对靶细胞的感染。核磁共振分析和分子动力学计算表明，T140具有由反平行β-折叠和II'型β-转角构成的刚性结构构象。在β-折叠的一侧，由三个氨基酸残基（L-3-(2-萘基)丙氨酸、Tyr5和Arg14）的侧链官能团形成一个突出部，每个残基对于强大的抗HIV活性都是不可或缺的。这些发现为剖析该化合物阻断CXCR4与T嗜性HIV-1毒株包膜糖蛋白之间相互作用的能力的结构基础提供了理论依据。
