微小核糖核酸的化学分子探针
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- 英文论文题名：Chemical Probes for MicroRNAs
- 论文作者：黄磊 ; 肖潇 ; 王星星 ; 陈颖捷 ; 李金波 ; 张艳
- 英文论文作者：Lei Huang ; Xiao Xiao ; Xingxing Wang ; Yingjie Chen ; Jinbo Li ; Yan Zhang ; School of Chemistry and Chemical Engineering ; Nanjing University
- 年：2016
- 作者机构：南京大学化学化工学院;
- 论文关键词：分子探针 ; 生物正交反应 ; 微小核糖核酸
- 会议召开时间：2016-07-01
- 会议录名称：中国化学会第30届学术年会摘要集-第二十八分会：化学生物学
- 语种：中文
- 分类号：O629.74
- 学会代码：ZGHY
- 会议名称：中国化学会第30届学术年会-第二十八分会 ; 化学生物学
- 会议地点：中国辽宁大连
- 主办单位：中国化学会
- 学会名称：中国化学会
- 页数：1
- 文件大小：140k
- 原文格式：D
- 会议级别：全国
摘要
微小核糖核酸是一类长约22个核苷酸的小分子核酸,其可在转录后水平对基因表达进行负调控。微小核糖核酸的异常表达已经被证实与疾病的发生发展密切相关,针对微小核糖核酸的化学生物学研究将为探索细胞内微小核糖核酸的信号网络及治疗与之相关的疾病提供有效的信息。基于对微小核糖核酸具有调控活性的化学小分子及微小核糖核酸类似物,我们在这些分子上修饰上不同的生物正交官能团,得到了不同类型的针对微小核糖核酸的化学分子探针。以对肌肉特异性微小核糖核酸具有选择性抑制活性的小分子为探针,我们发现了肌肉细胞内一条全新的信号通路。而以对微小核糖核酸具有广谱抑制活性的小分子为探针,我们结合生物正交反应揭示了其具体的作用机制。以微小核糖核酸类似物为探针并结合生物正交反应,我们实现了细胞内微小核糖核酸靶基因的鉴定及微小核糖核酸的时空分辨成像。而以靶向型阳离子多肽为载体,我们也实现了细胞外微小核糖核酸类似物向特定细胞的靶向输运。
A series of chemical probes for miRNAs based on active small molecules and oligonucleotides were developed by us.By high-throughput screening,two active small molecules that can specially inhibit myogenic miRNAs(myomiRs) and universally inhibit miRNAs were discovered.Small-molecule probes toward miRNAs were then developed by modifying these active small molecules with bio-orthogonal groups.In combination with bio-orthogonal chemistry,unknown myomiRs network and protein targets of these chemical probes were successfully unveiled.Oligonucleotides with same sequence of endogenous miRNAs were also modified with bio-orthogonal groups and turned into novel chemical probes for miRNAs.Through bio-orthogonal chemistry,miRNAs were successfully in-situ imaged in living cells and miRNA complexes were pulled down from cell lysis for further analysis.In addition,miRNAs were also delivered into cytoplasm with different chemical carriers for therapeutic treatment.Collectively,novel chemical probes based on small molecules and oligonucleotides were developed and applied to explore corresponding miRNAs with the help of different chemical strategies.
A series of chemical probes for miRNAs based on active small molecules and oligonucleotides were developed by us.By high-throughput screening,two active small molecules that can specially inhibit myogenic miRNAs(myomiRs) and universally inhibit miRNAs were discovered.Small-molecule probes toward miRNAs were then developed by modifying these active small molecules with bio-orthogonal groups.In combination with bio-orthogonal chemistry,unknown myomiRs network and protein targets of these chemical probes were successfully unveiled.Oligonucleotides with same sequence of endogenous miRNAs were also modified with bio-orthogonal groups and turned into novel chemical probes for miRNAs.Through bio-orthogonal chemistry,miRNAs were successfully in-situ imaged in living cells and miRNA complexes were pulled down from cell lysis for further analysis.In addition,miRNAs were also delivered into cytoplasm with different chemical carriers for therapeutic treatment.Collectively,novel chemical probes based on small molecules and oligonucleotides were developed and applied to explore corresponding miRNAs with the help of different chemical strategies.
引文
[1]Li,J.;Tan,S.;Kooger,R.;Zhang,C.;Zhang,Y.Chem.Soc.Rev.2014,43,506-517.
[2]Tan,S.~#;Li,J.~#;Chen,X.;Zhang,W.;Zhang,D.;Zhang,C.;Li,D.;Zhang,Y.Cell Chem.Biol.2014,21,1265-1270.
[2]Tan,S.~#;Li,J.~#;Chen,X.;Zhang,W.;Zhang,D.;Zhang,C.;Li,D.;Zhang,Y.Cell Chem.Biol.2014,21,1265-1270.