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Footprinting and circular dichroism studies on paromomycin binding to the packaging region of human immunodeficiency virus type-1.巴龙霉素与人免疫缺陷病毒1型包装区域结合的足迹法和圆二色性研究。
Bioorg Med Chem. 2002 Nov;10(11):3663-72. doi: 10.1016/s0968-0896(02)00220-1.
2
Absorption studies on aminoglycoside binding to the packaging region of human immunodeficiency virus type-1.氨基糖苷类与人类免疫缺陷病毒1型包装区域结合的吸收研究。
Bioorg Med Chem Lett. 2002 Feb 25;12(4):615-8. doi: 10.1016/s0960-894x(01)00823-x.
3
Binding of aminoglycoside antibiotics with modified A-site 16S rRNA construct containing non-nucleotide linkers.氨基糖苷类抗生素与含有非核苷酸接头的修饰A位点16S rRNA构建体的结合。
Bioorg Med Chem Lett. 2002 Feb 11;12(3):365-70. doi: 10.1016/s0960-894x(01)00760-0.
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2-Aminopurine as a real-time probe of enzymatic cleavage and inhibition of hammerhead ribozymes.2-氨基嘌呤作为锤头状核酶酶切和抑制的实时探针。
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关于新霉素B与人免疫缺陷病毒1型RNA包装区域结合的足迹法、圆二色性和紫外熔解研究。

Footprinting, circular dichroism and UV melting studies on neomycin B binding to the packaging region of human immunodeficiency virus type-1 RNA.

作者信息

McPike Mark P, Sullivan Julie M, Goodisman Jerry, Dabrowiak James C

机构信息

Department of Chemistry, Center for Science and Technology, Room 1-014, Syracuse University, Syracuse, NY 13244-4100, USA.

出版信息

Nucleic Acids Res. 2002 Jul 1;30(13):2825-31. doi: 10.1093/nar/gkf402.

DOI:10.1093/nar/gkf402
PMID:12087166
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC117057/
Abstract

We have studied the binding of neomycin to a 171mer RNA (psi-RNA) from the packaging region of the LAI strain of human immunodeficiency virus type-1, HIV-1 (LAI). The RNase I footprinting studies reveal that the primary binding site for the drug is in stem-loop 1, which contains the dimer initiation site of HIV-1. Loading this site with neomycin causes a structural change in the RNA, allowing nucleotides in the neighboring stem-loop 2 to participate in the drug site. Drug binding to secondary sites induces structural changes in other stem-loops of the RNA. Footprinting plots, showing cutting at a site as a function of drug concentration, were analyzed using a two-state model to obtain relative site-specific binding constants. Circular dichroism measurements show that neomycin binding to psi-RNA changes the intensity of the strong negative CD band at 208 nm, confirming that neomycin induces structural changes. Melting studies of the RNA showed melting transitions in the absence of drug at 28.2, 37.2, 47.4, 55.5 and 60.8 degrees C. Only the first two were affected by drug binding, the reason for this being explained by our analysis.

摘要

我们研究了新霉素与人免疫缺陷病毒1型(HIV-1)LAI株包装区域的171聚体RNA(ψ-RNA)的结合情况。核糖核酸酶I足迹分析研究表明,该药物的主要结合位点位于茎环1,其中包含HIV-1的二聚体起始位点。用新霉素占据该位点会导致RNA发生结构变化,使相邻茎环2中的核苷酸参与药物结合位点。药物与二级位点的结合会诱导RNA其他茎环的结构变化。使用双态模型分析足迹图(显示切割位点随药物浓度的变化)以获得相对位点特异性结合常数。圆二色性测量表明,新霉素与ψ-RNA的结合改变了208nm处强负性CD带的强度,证实新霉素诱导了结构变化。RNA的熔解研究表明,在无药物情况下,RNA在28.2、37.2、47.4、55.5和60.8摄氏度出现熔解转变。只有前两个转变受药物结合影响,我们的分析解释了其原因。