首页 | 本学科首页   官方微博 | 高级检索  
   检索      


Improved guanide compounds which bind the CXCR4 co-receptor and inhibit HIV-1 infection
Authors:Royce A Wilkinson  Seth H Pincus  Kejing Song  Joyce B Shepard  Alan J Weaver  Mohamed E Labib  Martin Teintze
Institution:1. Department of Chemistry & Biochemistry, 155 Chemistry & Biochemistry Building, Montana State University, Bozeman, MT 59717, United States;2. Research Institute for Children, Children’s Hospital, New Orleans, LA 70118, United States;3. Department of Pediatrics, LSU Health Sciences Center, New Orleans, LA 70118, United States;4. Novaflux Biosciences, Inc., Princeton, NJ 08540, United States
Abstract:The G-protein coupled receptor CXCR4 is a co-receptor for HIV-1 infection and is involved in signaling cell migration and proliferation. In a previous study of non-peptide, guanide-based CXCR4-binding compounds, spermine and spermidine phenylguanides inhibited HIV-1 entry at low micromolar concentrations. Subsequently, crystal structures of CXCR4 were used to dock a series of naphthylguanide derivatives of the polyamines spermidine and spermine. Synthesis and evaluation of the naphthylguanide compounds identified our best compound, spermine tris-1-naphthylguanide, which bound CXCR4 with an IC50 of 40 nM and inhibited the infection of TZM-bl cells with X4, but not R5, strains of HIV-1 with an IC50 of 50–100 nM.
Keywords:
本文献已被 ScienceDirect 等数据库收录!
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号