含荧光核碱基[双-o-(氨乙氧基)苯基]吡咯胞嘧啶的肽核酸寡聚物对突变型亨廷顿蛋白的细胞定位和等位基因选择性抑制。
Cellular localization and allele-selective inhibition of mutant huntingtin protein by peptide nucleic acid oligomers containing the fluorescent nucleobase [bis-o-(aminoethoxy)phenyl]pyrrolocytosine.
机构信息
Department of Pharmacology, UT Southwestern Medical Center at Dallas, Dallas, 6001 Forest Park Road, TX 75390, USA.
出版信息
Bioorg Med Chem Lett. 2009 Nov 1;19(21):6181-4. doi: 10.1016/j.bmcl.2009.09.004. Epub 2009 Sep 6.
Abstract
Peptide nucleic acid (PNA) is a successful DNA/RNA mimic. A major challenge for research is to invent chemically modified PNAs that retain the favorable properties of the parent compound while improving biological recognition. Here, we test modified PNAs containing [bis-o-(aminoethoxy)phenyl]pyrrolocytosine bases designed to engage guanine with an additional hydrogen bond. We observe elevated melting temperatures, localization to cellular compartments, and allele-selective inhibition of mutant huntingtin protein expression.
摘要
肽核酸（PNA）是一种成功的 DNA/RNA 模拟物。研究的一个主要挑战是发明化学修饰的 PNA，使其保留母体化合物的有利性质，同时改善生物识别。在这里，我们测试了含有[双-o-(氨乙氧基)苯基]吡咯胞嘧啶碱基的修饰 PNA，这些碱基旨在与额外的氢键结合鸟嘌呤。我们观察到了升高的熔点、细胞区室定位和等位基因选择性抑制突变亨廷顿蛋白表达。
相似文献
1
Cellular localization and allele-selective inhibition of mutant huntingtin protein by peptide nucleic acid oligomers containing the fluorescent nucleobase [bis-o-(aminoethoxy)phenyl]pyrrolocytosine.含荧光核碱基[双-o-(氨乙氧基)苯基]吡咯胞嘧啶的肽核酸寡聚物对突变型亨廷顿蛋白的细胞定位和等位基因选择性抑制。
Bioorg Med Chem Lett. 2009 Nov 1;19(21):6181-4. doi: 10.1016/j.bmcl.2009.09.004. Epub 2009 Sep 6.
2
Fluorescence and hybridization properties of peptide nucleic acid containing a substituted phenylpyrrolocytosine designed to engage Guanine with an additional H-bond.含取代苯基吡咯并胞嘧啶的肽核酸的荧光和杂交特性，该取代苯基吡咯并胞嘧啶旨在通过额外的氢键与鸟嘌呤结合。
J Am Chem Soc. 2008 Sep 24;130(38):12574-5. doi: 10.1021/ja804233g. Epub 2008 Aug 30.
3
Exceptional fluorescence and hybridization properties of a phenylpyrrolocytosine in peptide nucleic acid.苯基吡咯并胞嘧啶在肽核酸中的优异荧光和杂交特性。
Nucleic Acids Symp Ser (Oxf). 2008(52):401-2. doi: 10.1093/nass/nrn204.
4
Peptide nucleic acid containing a meta-substituted phenylpyrrolocytosine exhibits a fluorescence response and increased binding affinity toward RNA.含有间位取代苯基吡咯并胞嘧啶的肽核酸表现出荧光响应并增强了对RNA的结合亲和力。
Org Lett. 2009 Nov 5;11(21):4878-81. doi: 10.1021/ol9019474.
5
High-affinity peptide nucleic acid oligomers containing tricyclic cytosine analogues.含有三环胞嘧啶类似物的高亲和力肽核酸低聚物。
Org Lett. 2002 Dec 12;4(25):4395-8. doi: 10.1021/ol027026a.
6
Allele-selective inhibition of mutant huntingtin by peptide nucleic acid-peptide conjugates, locked nucleic acid, and small interfering RNA.肽核酸-肽偶联物、锁核酸和小干扰RNA对突变亨廷顿蛋白的等位基因选择性抑制作用
Ann N Y Acad Sci. 2009 Sep;1175:24-31. doi: 10.1111/j.1749-6632.2009.04975.x.
7
Properties of a new fluorescent cytosine analogue, pyrrolocytosine.一种新型荧光胞嘧啶类似物——吡咯胞嘧啶的性质
J Phys Chem B. 2005 Mar 31;109(12):6012-9. doi: 10.1021/jp046177n.
8
Incorporation of thio-pseudoisocytosine into triplex-forming peptide nucleic acids for enhanced recognition of RNA duplexes.将硫代假异胞嘧啶掺入三链形成肽核酸中以增强对RNA双链体的识别。
Nucleic Acids Res. 2014 Apr;42(6):4008-18. doi: 10.1093/nar/gkt1367. Epub 2014 Jan 13.
9
1,8-Naphthyridin-2,7-(1,8H)-dione is an effective mimic of protonated cytosine in peptide nucleic acid triplex recognition systems.1,8-萘啶-2,7-(1,8H)-二酮是肽核酸三链体识别系统中质子化胞嘧啶的有效模拟物。
Bioorg Med Chem Lett. 2002 Nov 4;12(21):3121-4. doi: 10.1016/s0960-894x(02)00658-3.
10
Allele-selective inhibition of expression of huntingtin and ataxin-3 by RNA duplexes containing unlocked nucleic acid substitutions.含非锁核酸取代的 RNA 双链体对亨廷顿蛋白和 ataxin-3 表达的等位基因选择性抑制。
Biochemistry. 2013 Dec 23;52(51):9329-38. doi: 10.1021/bi4014209. Epub 2013 Nov 27.
引用本文的文献
1
Thyclotides, tetrahydrofuran-modified peptide nucleic acids that efficiently penetrate cells and inhibit microRNA-21.噻咯肽，四氢呋喃修饰的肽核酸，能有效穿透细胞并抑制 microRNA-21。
Nucleic Acids Res. 2022 Oct 28;50(19):10839-10856. doi: 10.1093/nar/gkac864.
2
Chromatin accessibility and transcription dynamics during in vitro astrocyte differentiation of Huntington's Disease Monkey pluripotent stem cells.亨廷顿病猴多能干细胞体外分化为星形胶质细胞过程中的染色质可及性和转录动态。
Epigenetics Chromatin. 2019 Nov 13;12(1):67. doi: 10.1186/s13072-019-0313-6.
3
Fluorogenic PNA probes.荧光肽核酸探针。
Beilstein J Org Chem. 2018 Jan 29;14:253-281. doi: 10.3762/bjoc.14.17. eCollection 2018.
4
Gene suppression approaches to neurodegeneration.神经退行性疾病的基因抑制方法。
Alzheimers Res Ther. 2017 Oct 5;9(1):82. doi: 10.1186/s13195-017-0307-1.
5
Gene suppression strategies for dominantly inherited neurodegenerative diseases: lessons from Huntington's disease and spinocerebellar ataxia.显性遗传神经退行性疾病的基因抑制策略：来自亨廷顿舞蹈症和脊髓小脑共济失调的经验教训
Hum Mol Genet. 2016 Apr 15;25(R1):R53-64. doi: 10.1093/hmg/ddv442. Epub 2015 Oct 26.
6
Antisense therapy in neurology.神经科的反义治疗。
J Pers Med. 2013 Aug 2;3(3):144-76. doi: 10.3390/jpm3030144.
7
Phosphorodiamidate morpholino oligomers suppress mutant huntingtin expression and attenuate neurotoxicity.磷酰二胺吗啉代寡聚物可抑制突变型亨廷顿蛋白的表达并减轻神经毒性。
Hum Mol Genet. 2014 Dec 1;23(23):6302-17. doi: 10.1093/hmg/ddu349. Epub 2014 Jul 4.
8
Small non-coding RNAs add complexity to the RNA pathogenic mechanisms in trinucleotide repeat expansion diseases.小非编码RNA增加了三核苷酸重复扩增疾病中RNA致病机制的复杂性。
Front Mol Neurosci. 2013 Dec 3;6:45. doi: 10.3389/fnmol.2013.00045.
9
Chemical structure requirements and cellular targeting of microRNA-122 by peptide nucleic acids anti-miRs.肽核酸抗 miR 对 microRNA-122 的化学结构要求和细胞靶向作用。
Nucleic Acids Res. 2012 Mar;40(5):2152-67. doi: 10.1093/nar/gkr885. Epub 2011 Nov 8.
10
Allele-selective inhibition of ataxin-3 (ATX3) expression by antisense oligomers and duplex RNAs.反义寡核苷酸和双链 RNA 对 ATX3 表达的等位基因选择性抑制。
Biol Chem. 2011 Apr;392(4):315-25. doi: 10.1515/BC.2011.045. Epub 2011 Feb 7.
本文引用的文献
1
Fluorescein redirects a ruthenium-octaarginine conjugate to the nucleus.荧光素将钌 - 八聚精氨酸共轭物重定向至细胞核。
J Am Chem Soc. 2009 Jul 1;131(25):8738-9. doi: 10.1021/ja9025165.
2
Locked nucleic acid as a novel class of therapeutic agents.锁核酸作为一类新型治疗剂。
RNA Biol. 2009 Jul-Aug;6(3):321-3. doi: 10.4161/rna.6.3.8807. Epub 2009 Jul 18.
3
Allele-specific silencing of mutant huntingtin and ataxin-3 genes by targeting expanded CAG repeats in mRNAs.通过靶向mRNA中扩增的CAG重复序列实现突变型亨廷顿蛋白和ataxin-3基因的等位基因特异性沉默。
Nat Biotechnol. 2009 May;27(5):478-84. doi: 10.1038/nbt.1539. Epub 2009 May 3.
4
Fluorescence and hybridization properties of peptide nucleic acid containing a substituted phenylpyrrolocytosine designed to engage Guanine with an additional H-bond.含取代苯基吡咯并胞嘧啶的肽核酸的荧光和杂交特性，该取代苯基吡咯并胞嘧啶旨在通过额外的氢键与鸟嘌呤结合。
J Am Chem Soc. 2008 Sep 24;130(38):12574-5. doi: 10.1021/ja804233g. Epub 2008 Aug 30.
5
Improved cellular activity of antisense peptide nucleic acids by conjugation to a cationic peptide-lipid (CatLip) domain.通过与阳离子肽-脂质（CatLip）结构域偶联提高反义肽核酸的细胞活性。
Bioconjug Chem. 2008 Aug;19(8):1526-34. doi: 10.1021/bc800068h. Epub 2008 Jul 23.
6
miR-122 targeting with LNA/2'-O-methyl oligonucleotide mixmers, peptide nucleic acids (PNA), and PNA-peptide conjugates.使用锁核酸/2'-O-甲基寡核苷酸混合体、肽核酸（PNA）以及PNA-肽缀合物靶向作用于miR-122 。
RNA. 2008 Feb;14(2):336-46. doi: 10.1261/rna.844108. Epub 2007 Dec 11.
7
Cell penetrating peptide conjugates of steric block oligonucleotides.空间位阻寡核苷酸的细胞穿透肽缀合物
Adv Drug Deliv Rev. 2008 Mar 1;60(4-5):517-29. doi: 10.1016/j.addr.2007.09.002. Epub 2007 Oct 22.
8
Inhibiting gene expression with peptide nucleic acid (PNA)--peptide conjugates that target chromosomal DNA.使用靶向染色体DNA的肽核酸（PNA）-肽缀合物抑制基因表达。
Biochemistry. 2007 Jun 26;46(25):7581-9. doi: 10.1021/bi700230a. Epub 2007 May 31.
9
Flow cytometry and FISH to measure the average length of telomeres (flow FISH).采用流式细胞术和荧光原位杂交技术来测量端粒的平均长度（流式荧光原位杂交技术）。
Nat Protoc. 2006;1(5):2365-76. doi: 10.1038/nprot.2006.263.
10
Huntington's disease.亨廷顿舞蹈症
Lancet. 2007 Jan 20;369(9557):218-28. doi: 10.1016/S0140-6736(07)60111-1.
Zotero 插件