Dipartimento di Chimica Organica e Industriale and CISI, Universita degli Studi di Milano, Italy.
ACS Chem Biol. 2010 Mar 19;5(3):301-12. doi: 10.1021/cb900216e.
HIV infection is pandemic in humans and is responsible for millions of deaths every year. The discovery of new cellular targets that can be used to prevent the infection process represents a new opportunity for developing more effective antiviral drugs. In this context, dendritic cell-specific ICAM-3 grabbing non-integrin (DC-SIGN), a lectin expressed at the surface of immature dendritic cells and involved in the initial stages of HIV infection, is a promising therapeutic target. Herein we show the ability of a new tetravalent dendron containing four copies of a linear trimannoside mimic to inhibit the trans HIV infection process of CD4+ T lymphocytes at low micromolar range. This compound presents a high solubility in physiological media, a neglectable cytotoxicity, and a long-lasting effect and is based on carbohydrate-mimic units. Notably, the HIV antiviral activity is independent of viral tropism (X4 or R5). The formulation of this compound as a gel could allow its use as topical microbicide.
HIV 感染在人类中是全球性的，每年导致数百万人死亡。发现新的细胞靶标，可用于预防感染过程，为开发更有效的抗病毒药物提供了新的机会。在这种情况下，树突状细胞特异性细胞间黏附分子-3 抓取非整合素（DC-SIGN）是一种在未成熟树突状细胞表面表达的凝集素，参与 HIV 感染的早期阶段，是一个很有前途的治疗靶点。本文展示了一种新型四价树突，其中包含四个线性三糖类似物的拷贝，能够以低微摩尔浓度抑制 CD4+T 淋巴细胞的 HIV 转染感染过程。该化合物在生理介质中具有高溶解度、可忽略的细胞毒性、持久的效果，并且基于碳水化合物模拟物单元。值得注意的是，该化合物的抗 HIV 活性与病毒嗜性（X4 或 R5）无关。将该化合物制成凝胶制剂，可作为局部杀微生物剂使用。
