Ju Tong, Hu Duoyi, Xiang Shi-Hua, Guo Jiantao
Department of Chemistry, University of Nebraska-Lincoln, Lincoln, NE 68588, United States.
Nebraska Center for Virology, School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, NE 68588, United States.
Bioorg Chem. 2016 Oct;68:105-11. doi: 10.1016/j.bioorg.2016.07.012. Epub 2016 Jul 25.
Human immunodeficiency virus type 1 (HIV-1) is responsible for the worldwide AIDS pandemic. Due to the lack of prophylactic HIV-1 vaccine, drug treatment of the infected patients becomes essential to reduce the viral load and to slow down progression of the disease. Because of drug resistance, finding new antiviral agents is necessary for AIDS drug therapies. The interaction of gp120 and co-receptor (CCR5/CXCR4) mediates the entry of HIV-1 into host cells, which has been increasingly exploited in recent years as the target for new antiviral agents. A conserved co-receptor binding site on gp120 that recognizes sulfotyrosine (sTyr) residues represents a structural target to design novel HIV entry inhibitors. In this work, we developed an efficient synthesis of sulfotyrosine dipeptide and evaluated it as an HIV-1 entry inhibitor.
1型人类免疫缺陷病毒(HIV-1)是全球艾滋病大流行的罪魁祸首。由于缺乏预防性HIV-1疫苗,对感染患者进行药物治疗对于降低病毒载量和减缓疾病进展至关重要。由于耐药性的存在,寻找新的抗病毒药物对于艾滋病药物治疗来说是必要的。gp120与共受体(CCR5/CXCR4)的相互作用介导HIV-1进入宿主细胞,近年来这一过程越来越多地被用作新型抗病毒药物的靶点。gp120上一个识别磺基酪氨酸(sTyr)残基的保守共受体结合位点是设计新型HIV进入抑制剂的结构靶点。在这项工作中,我们开发了一种高效合成磺基酪氨酸二肽的方法,并将其作为HIV-1进入抑制剂进行了评估。