新型 dsDNA 端帽间隔物的合成与评价。

Synthesis and evaluation of new spacers for use as dsDNA end-caps.

机构信息

Department of Medicinal Chemistry and Molecular Pharmacology, Department of Biological Sciences, and Bindley Bioscience Center, Purdue University, 1205 W State St., West Lafayette, IN 47907, USA.

出版信息

Bioconjug Chem. 2010 Aug 18;21(8):1545-53. doi: 10.1021/bc100202y.

DOI:10.1021/bc100202y

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2933660/

Abstract

A series of aliphatic and aromatic spacer molecules designed to cap the ends of DNA duplexes have been synthesized. The spacers were converted into dimethoxytrityl-protected phosphoramidites as synthons for oligonucleotides synthesis. The effect of the spacers on the stability of short DNA duplexes was assessed by melting temperature studies. End-caps containing amide groups were found to be less stabilizing than the hexaethylene glycol spacer. End-caps containing either a terthiophene or a naphthalene tetracarboxylic acid diimide were found to be significantly more stabilizing. The former showed a preference for stacking above an A*T base pair. Spacers containing only methylene (-CH(2)-) and amide (-CONH-) groups interact weakly with DNA and consequently may be optimal for applications that require minimal influence on DNA structure but require a way to hold the ends of double-stranded DNA together.

摘要

已经合成了一系列设计用于封闭 DNA 双链末端的脂肪族和芳香族间隔分子。这些间隔物被转化为二甲氧基三苯甲基保护的亚磷酰胺作为寡核苷酸合成的前体。通过熔点研究评估了间隔物对短 DNA 双链稳定性的影响。含有酰胺基团的端基比六亚乙基二醇间隔物的稳定性差。含有三噻吩或萘四羧酸二酰亚胺的端基被发现具有显著更高的稳定性。前者显示出在 A*T 碱基对上堆积的偏好。仅含有亚甲基（-CH(2)-）和酰胺（-CONH-）基团的间隔物与 DNA 弱相互作用，因此可能是需要对 DNA 结构的最小影响但需要一种方法将双链 DNA 的末端保持在一起的应用的最佳选择。

相似文献

1

Synthesis and evaluation of new spacers for use as dsDNA end-caps.

Bioconjug Chem. 2010 Aug 18;21(8):1545-53. doi: 10.1021/bc100202y.

2

Synthesis of endcap dimethoxytrityl phosphoramidites for endcapped oligonucleotides.

Curr Protoc Nucleic Acid Chem. 2003 May;Chapter 5:Unit 5.6. doi: 10.1002/0471142700.nc0506s12.

3

Efficient cleavage of DS DNA by bleomycin conjugated via hexaethylene glycol linker to triplex-forming oligonucleotides.

Nucleosides Nucleotides Nucleic Acids. 2004 Oct;23(6-7):1047-51. doi: 10.1081/NCN-200026066.

4

Synthesis of oligonucleotides with a 2'-cap at the 3'-terminus via reversed phosphoramidites.

Org Lett. 2003 Feb 6;5(3):247-50. doi: 10.1021/ol020212w.

5

Observation and elimination of N-acetylation of oligonucleotides prepared using fast-deprotecting phosphoramidites and ultra-mild deprotection.

Bioorg Med Chem Lett. 2001 May 7;11(9):1105-7. doi: 10.1016/s0960-894x(01)00161-5.

6

Tandem oligonucleotide synthesis using linker phosphoramidites.

Nucleic Acids Res. 2005 Apr 6;33(6):1940-8. doi: 10.1093/nar/gki333. Print 2005.

7

[Oligonucleotide derivatives in the nucleic acid hybridization analysis. III. Synthesis and investigation of properties of oligonucleotides, bearing bifunctional non-nucleotide insert].

Bioorg Khim. 2012 Nov-Dec;38(6):706-20.

8

Azide-alkyne "click" conjugation of 8-aza-7-deazaadenine-DNA: synthesis, duplex stability, and fluorogenic dye labeling.

Bioconjug Chem. 2010 Sep 15;21(9):1629-41. doi: 10.1021/bc100090y.

9

Synthesis of the first tellurium-derivatized oligonucleotides for structural and functional studies.

Chemistry. 2009 Oct 5;15(39):10210-6. doi: 10.1002/chem.200900774.

10

Oligonucleotides with 2'-O-carboxymethyl group: synthesis and 2'-conjugation via amide bond formation on solid phase.

Org Biomol Chem. 2004 Oct 7;2(19):2793-7. doi: 10.1039/B409496D. Epub 2004 Sep 3.

引用本文的文献

1

Stabilization of RNA hairpins using non-nucleotide linkers and circularization.

Nucleic Acids Res. 2017 Jun 2;45(10):e92. doi: 10.1093/nar/gkx122.

2

Hydrophobic organic linkers in the self-assembly of small molecule-DNA hybrid dimers: a computational-experimental study of the role of linkage direction in product distributions and stabilities.

J Phys Chem B. 2014 Mar 6;118(9):2366-76. doi: 10.1021/jp501041m. Epub 2014 Feb 21.

3

Evaluation of end-capped DNA modules for pRNA capture and functionalization.

Bioconjug Chem. 2012 Apr 18;23(4):683-7. doi: 10.1021/bc200371t. Epub 2012 Apr 9.

本文引用的文献

1

Hydrophobic dimerization and thermal dissociation of perylenediimide-linked DNA hairpins.

J Am Chem Soc. 2009 Apr 29;131(16):5920-9. doi: 10.1021/ja900347t.

2

Synthesis of endcap dimethoxytrityl phosphoramidites for endcapped oligonucleotides.

Curr Protoc Nucleic Acid Chem. 2003 May;Chapter 5:Unit 5.6. doi: 10.1002/0471142700.nc0506s12.

3

How much pi-stacking do DNA termini seek? Solution structure of a self-complementary DNA hexamer with trimethoxystilbenes capping the terminal base pairs.

Biochemistry. 2004 Dec 21;43(50):15680-7. doi: 10.1021/bi048205y.

4

Protein-DNA footprinting by endcapped duplex oligodeoxyribonucleotides.

Nucleic Acids Res. 2004 Jul 19;32(13):e107. doi: 10.1093/nar/gnh103.

5

Endcaps for stabilizing short DNA duplexes.

Nucleosides Nucleotides Nucleic Acids. 2003 May-Aug;22(5-8):1635-7. doi: 10.1081/NCN-120023088.

6

DNA polymerase template interactions probed by degenerate isosteric nucleobase analogs.

Chem Biol. 2003 Sep;10(9):815-25. doi: 10.1016/j.chembiol.2003.08.008.

7

Face-to-face and edge-to-face pi-pi interactions in a synthetic DNA hairpin with a stilbenediether linker.

J Am Chem Soc. 2003 Sep 10;125(36):10842-9. doi: 10.1021/ja0355527.

8

Synthesis, structure, and photochemistry of exceptionally stable synthetic DNA hairpins with stilbene diether linkers.

J Am Chem Soc. 2002 Oct 16;124(41):12165-73. doi: 10.1021/ja026941o.

9

Preorganization of DNA: Design Principles for Improving Nucleic Acid Recognition by Synthetic Oligonucleotides.

Chem Rev. 1997 Aug 5;97(5):1473-1488. doi: 10.1021/cr9603791.

10

Crystal structures of a ddATP-, ddTTP-, ddCTP, and ddGTP- trapped ternary complex of Klentaq1: insights into nucleotide incorporation and selectivity.

Protein Sci. 2001 Jun;10(6):1225-33. doi: 10.1110/ps.250101.

文献AI研究员

20分钟写一篇综述，助力文献阅读效率提升50倍。

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

文档翻译

学术文献翻译模型，支持多种主流文档格式。