Institute of Biomolecular Chemistry, CNR, Padova Unit, Department of Chemistry University of Padova via Marzolo 1, 35131 Padova, Italy.
Chemistry. 2010 Jan 4;16(1):316-27. doi: 10.1002/chem.200900945.
Integramide A is a 16-amino acid peptide inhibitor of the enzyme HIV-1 integrase. We have recently reported that the absolute stereochemistries of the dipeptide sequence near the C terminus are L-Iva(14)-D-Iva(15). Herein, we describe the syntheses of the natural compound and its D-Iva(14)-L-Iva(15) diastereomer, and the results of their chromatographic/mass spectrometric analyses. We present the conformational analysis of the two compounds and some of their synthetic intermediates of different main-chain length in the crystal state (by X-ray diffraction) and in solvents of different polarities (using circular dichroism, FTIR absorption, and 2D NMR techniques). These data shed light on the mechanism of inhibition of HIV-1 integrase, which is an important target for anti-HIV therapy.
Integramide A 是一种 16 个氨基酸的肽类 HIV-1 整合酶抑制剂。我们最近报道了 C 末端附近二肽序列的绝对立体化学结构为 L-Iva(14)-D-Iva(15)。在此，我们描述了天然化合物及其 D-Iva(14)-L-Iva(15)非对映异构体的合成，并报告了它们的色谱/质谱分析结果。我们展示了这两种化合物及其不同主链长度的一些合成中间体在晶体状态（通过 X 射线衍射）和不同极性溶剂（使用圆二色性、FTIR 吸收和 2D NMR 技术）中的构象分析。这些数据阐明了 HIV-1 整合酶抑制的机制，这是抗 HIV 治疗的一个重要靶点。
