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国家自然科学基金(20332010)

作品数:5 被引量:5H指数:1
相关作者:张礼和张亮仁杨振军任博刘迎春更多>>
相关机构:北京大学更多>>
发文基金:国家自然科学基金国家重点基础研究发展计划更多>>
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HIV-1整合酶的RNA适配子的筛选及活性研究被引量:4
2008年
通过SELEX技术已经筛选到了多种HIV-1病毒相关蛋白,如:逆转录酶、Rev和Tat蛋白、核壳蛋白等的核酸适配子,然而以HIV-1整合酶为靶点的DNA或RNA适配子却鲜有报道.在结合缓冲液中以10mmol·L-1的Mg2+作为辅助因子,加入100mmol·L-1KCl筛选到了三个具有相似结构和Kd的适配子IN1,IN2和IN3.亲和力最高的适配子IN1的Kd为145nmol·L-1,保守区富含鸟嘌呤碱基(G),缺失任何一个茎环结构会使亲和力减弱.缺失右端固定序列的IN1-L的Kd为283nmol·L-1,虽然不能形成四链结构但可以被G-四链T40214竞争结合,可能与T40214具有相同的结合位点.
刘迎春张艳叶国柱杨振军张亮仁张礼和
关键词:HIV-1整合酶
基于Click反应的肽缀合小干扰RNA(siRNA)的固相合成
<正>小干扰RNA(siRNA)的跨膜转运是当前生物医学研究领域研究的重大课题之一,合理有效的转运系统可以显著提高siRNA的生理作用。有研究表明多肽片段有助于siRNA透过细胞膜甚至血脑屏障,本文以信号肽片段与siRN...
刘洋杨振军张亮仁张礼和
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In vitro selection of G-rich RNA aptamers that target HIV-1 integrase
2008年
Aptamers that interact with various HIV-1 proteins,such as reverse transcriptase,Rev,Tat protein,and nuclear capsule protein,have been prepared through SELEX (systematic evolution of ligands by ex-ponential enrichment) technique. However,there are few reports about the DNA or RNA aptamers that target HIV-1 integrase. In this investigation,we selected alternative RNA aptamers specific for the HIV-1 integrase by using a different binding buffer containing 10 mmol·L-1 MgCl2 and 100 mmol·L-1 KCl. Aptamer IN1,IN2,IN3 had similar and the highest Kd values from 145 to 239 nmol·L-1. Structural studies showed that they formed similar stem-loop structure. Deletion of any stem structure resulted in diminished affinity. In addition,structure probing study with antisense DNA indicated that the stem-loop structure in the random region was critical for integrase binding. Although aptamer IN1 failed to form G-quartet structure,it might directly interact with the DDE motif of integrase,which is the virus DNA-binding site,because G-quadruplex T40214 competitively inhibited the interaction between IN1 and integrase. Together,this study generated a novel RNA aptamer IN1,which could be useful in basic research and anti-HIV drug screening.
LIU YingChunZHANG YanYE GuoZhuYANG ZhenJunZHANG LiangRenZHANG LiHe
关键词:APTAMERHIV-1INTEGRASEG-QUADRUPLEX
Two Concise Methods to Prepare Peptide-oligonucleotide Conjugates
<正>RNA interference(RNAi)has been rapid progress towards its application as one of the most important molecula...
Fei-Lin Nie Zhen-Jun Yang~* Liang-Ren Zhang Li-He Zhang State Key Laboratory of Natural and Biomimetic Drugs,School of Pharmaceutical Sciences,Peking University,Beijing100083
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Synthesis of nucleoside-peptide conjugate with disulfide bond as linker at C-5 of uridine
2008年
In order to prepare pyrimidine nucleoside-peptide conjugate concisely, we developed a one-pot synthetic strategy. Started from uridine, 5-S-acetyl-thiomethyl-2',3 '-di-O-isopropylidene-uridine (4) was synthesized as the key intermediate in four steps. Under acidic condition, compound 4 was deprotected and reacted with PySS-R (8, 12, 15, Py = 2-pyridyl, R = amino acid or peptide) in one pot to form uridine conjugates (9, 13, 2) with disulfide bond as linker.
聂菲璘王晓峰刘洋杨振军张亮仁张礼和
非胶毛细管电泳在HIV-1逆转录酶稳态动力学研究中的应用
<正>人类免疫缺陷病毒(human immunodeficiency virus,HIV)是AIDS的病原体,属于逆转录病毒科、慢病毒属中的灵长类免疫缺陷病毒亚属。AZT和d4T等上市的核苷类逆转录酶抑制剂,通过HIV-...
黎武杰曹眸裴璐关注凌笑梅杨振军
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Properties of Novel Antisense Oligonucleotides Containing Isoadenosine (isoA)
<正>Antisense oligonucleotides have been applied extensively for the regulation of cellular and viral gene expr...
Ren-Ping Qiao Jun Zhang Zhen-Jun Yang~* Liang-Ren Zhang Li-He Zhang State Key Laboratory of Natural and Biomimetic Drugs,School of Pharmaceutical Science,Peking University,Beijing 100083
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Microwave-assisted Intra-molecular Pyrophosphorylation at High Concentrations:An Efficient Approach for Synthesis of cTDPRE as the Nucleobase-simplifed cADPR Analogue
CADPR-mediated Ca signaling has received great attention in the fields of chemical synthesis and biological re...
Lingjun Li,~(1,2) Zhenjun Yang,~1 Liangren,Zhang,~1 and Lihe Zhang~(1*) 1 National Laboratory of Natural and Biomimetic Drugs,School of Pharmaceutical Sciences,Peking University,Beijing 100083
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Synthesis and biological evaluation of neamine analogues for RNA binding
2008年
To design and synthesize neamine analogues modified at 5 position offing Ⅱ, which could improve the binding affinity of aminoglycosides to 16S RNA. Started from neomycin B, modified neamine analogues were synthesized through organic reactions such as hydrolysis, protection, nucleophilic substitution, deprotection and reduction. The interaction of the target compounds with A-site RNA in E. coli. ribosome (16S RNA) was determined by surface plasmon resonance (SPR), respectively. Six target compounds were synthesized. Some of them showed antibacterial activities and enhanced affinity to 16S RNA at 10^-3M in vitro. Introduction amino or aliphatic amino group at 5 position offing Ⅱ in neamine would maintained antibacterial activities as well as increase binding affinity to 16S RNA. Furthermore, there is almost no influence on the stability of drug/16S RNA complex by inverting the configuration of 5-hydroxyl group at ring Ⅱ.
蔡黎任博张峰荣杨振军张亮仁张礼和
关键词:AMINOGLYCOSIDESPRANTIBACTERIAL
氨基糖苷类化合物与RNA相互作用的研究进展被引量:1
2004年
RNA已经成为重要的药物研究靶点 ,氨基糖苷类化合物是能够与RNA作用的小分子中较有潜力的一类化合物。
任博张礼和
关键词:RNA相互作用
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