• <code id="tvhzc"><ol id="tvhzc"></ol></code>
    <big id="tvhzc"><span id="tvhzc"></span></big>
  • <object id="tvhzc"><strong id="tvhzc"></strong></object>
    首頁> 外文期刊>Biochimica et Biophysica Acta. General Subjects >Anti-HIV-1 activity and structure-activity-relationship study of a fucosylated glycosaminoglycan from an echinoderm by targeting the conserved CD4 induced epitope
    【24h】

    Anti-HIV-1 activity and structure-activity-relationship study of a fucosylated glycosaminoglycan from an echinoderm by targeting the conserved CD4 induced epitope

    機譯:通過靶向保守的CD4誘導的表位,從棘皮動物的巖藻糖基化糖胺聚糖的抗HIV-1活性和結構-活性-關系研究

    獲取原文
    獲取原文并翻譯 | 示例
               

    摘要

    Background Fucosylated glycosaminoglycan (FG) is a novel glycosaminoglycan with a chondroitin sulfate-like backbone and fucose sulfate branches. The aim of this study is to investigate the mechanism and structure-activity relationships (SAR) of FG for combating HIV-1 infection. Methods Anti-HIV activities of FGs were assessed by a cytopathic effect assay and an HIV-1 p24 detection assay. The biomolecule interactions were explored via biolayer interferometry technology. The SAR was established by comparing its anti-HIV-1 activities, conserved CD4 induced (CD4i) epitope-dependent interactions and anticoagulant activities. Results FG efficiently and selectively inhibited the X4- and R5X4-tropic HIV-1 infections in C8166 cells with little cytotoxicity against C8166 cells and PBMCs. Our data indicated that FG bound to gp120 with nanomolar affinity and may interact with CD4i of gp120. Additionally, the CD4i binding affinity of FG was higher than that of dextran sulfate. SAR studies suggested that the unique sulfated fucose branches account for the anti-HIV-1 activity. The molecular size and present carboxyl groups of FG may also play important roles in various activities. Notably, several FG derivatives showed higher anti-HIV-1 activities and much lower anticoagulant activities than those of heparin. Conclusions FG exhibits strong activity against X4- and R5X4-tropic HIV-1 infections. The mechanism may be related to targeting CD4i of gp120, which results in inhibition of HIV-1 entry. The carboxyl group substituted derivatives of FG (8.5-12.8 kDa), might display high anti-HIV-1 activity and low anticoagulant activity. General significance Our data supports further the investigation of FG derivatives as novel HIV-1 entry inhibitors targeting CD4i.
    機譯:背景巖藻糖基糖胺聚糖(FG)是一種新型的糖胺聚糖,具有硫酸軟骨素樣骨架和硫酸巖藻糖分支。這項研究的目的是調查FG對抗HIV-1感染的機制和構效關系(SAR)。方法通過細胞病變效應測定和HIV-1 p24檢測測定來評估FGs的抗HIV活性。通過生物層干涉技術探索了生物分子的相互作用。通過比較其抗HIV-1活性,保守的CD4誘導的(CD4i)表位依賴性相互作用和抗凝血活性來建立SAR。結果FG有效和選擇性地抑制了C8166細胞中X4-和R5X4-嗜性HIV-1感染,而對C8166細胞和PBMC的細胞毒性很小。我們的數據表明,FG以納摩爾親和力與gp120結合,并可能與gp120的CD4i相互作用。另外,FG的CD4i結合親和力高于硫酸葡聚糖。 SAR研究表明,獨特的硫酸鹽巖藻糖分支是抗HIV-1活性的原因。 FG的分子大小和當前的羧基也可能在各種活動中起重要作用。值得注意的是,幾種FG衍生物比肝素具有更高的抗HIV-1活性和低得多的抗凝活性。結論FG對X4-和R5X4-tropic HIV-1感染表現出較強的活性。該機制可能與靶向gp120的CD4i有關,這導致HIV-1進入受到抑制。 FG(8.5-12.8 kDa)的羧基取代衍生物可能具有較高的抗HIV-1活性和較低的抗凝活性。一般意義我們的數據支持進一步研究FG衍生物作為靶向CD4i的新型HIV-1進入抑制劑。

    著錄項

    相似文獻

    • 外文文獻
    • 中文文獻
    • 專利
    獲取原文

    客服郵箱:kefu@zhangqiaokeyan.com

    京公網安備:11010802029741號 ICP備案號:京ICP備15016152號-6 六維聯合信息科技 (北京) 有限公司?版權所有
    • 客服微信

    • 服務號

    在线中文字幕日本无码欧美_国产萝控精品福利视频_2020黄色三级片电影_人妻系列在线亚洲
  • <code id="tvhzc"><ol id="tvhzc"></ol></code>
    <big id="tvhzc"><span id="tvhzc"></span></big>
  • <object id="tvhzc"><strong id="tvhzc"></strong></object>