缺乏2-酮基的嘧啶核苷酸类似物对DNA聚合酶反应的抑制作用。
Inhibition of DNA polymerase reactions by pyrimidine nucleotide analogues lacking the 2-keto group.
作者信息
Guo M J, Hildbrand S, Leumann C J, McLaughlin L W, Waring M J
机构信息
Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QJ, UK.
出版信息
Nucleic Acids Res. 1998 Apr 15;26(8):1863-9. doi: 10.1093/nar/26.8.1863.
Abstract
To investigate the influence of the pyrimidine 2-keto group on selection of nucleotides for incorporation into DNA by polymerases, we have prepared two C nucleoside triphosphates that are analogues of dCTP and dTTP, namely 2-amino-5-(2'-deoxy-beta-d-ribofuranosyl)pyridine-5'-triphosphate (dCTP) and 5-(2'-deoxy- beta-d-ribofuranosyl)-3-methyl-2-pyridone-5'-triphosphate (dTTP) respectively. Both proved strongly inhibitory to PCR catalysed by Taq polymerase; dTTP rather more so than dCTP. In primer extension experiments conducted with either Taq polymerase or the Klenow fragment of Escherichia coli DNA polymerase I, both nucleotides failed to substitute for their natural pyrimidine counterparts. Neither derivative was incorporated as a chain terminator. Their capacity to inhibit DNA polymerase activity may well result from incompatibility with the correctly folded form of the polymerase enzyme needed to stabilize the transition state and catalyse phosphodiester bond formation.
摘要
为了研究嘧啶2-酮基团对聚合酶将核苷酸掺入DNA时核苷酸选择的影响，我们制备了两种C核苷三磷酸，它们分别是dCTP和dTTP的类似物，即2-氨基-5-（2'-脱氧-β-D-呋喃核糖基）吡啶-5'-三磷酸（dCTP）和5-（2'-脱氧-β-D-呋喃核糖基）-3-甲基-2-吡啶酮-5'-三磷酸（dTTP）。两者均被证明对Taq聚合酶催化的PCR具有强烈抑制作用；dTTP的抑制作用比dCTP更强。在用Taq聚合酶或大肠杆菌DNA聚合酶I的Klenow片段进行的引物延伸实验中，两种核苷酸都不能替代它们天然的嘧啶对应物。两种衍生物都不能作为链终止剂掺入。它们抑制DNA聚合酶活性的能力很可能是由于与稳定过渡态和催化磷酸二酯键形成所需的正确折叠形式的聚合酶不相容所致。
相似文献
1
Inhibition of DNA polymerase reactions by pyrimidine nucleotide analogues lacking the 2-keto group.缺乏2-酮基的嘧啶核苷酸类似物对DNA聚合酶反应的抑制作用。
Nucleic Acids Res. 1998 Apr 15;26(8):1863-9. doi: 10.1093/nar/26.8.1863.
2
Nucleoside analogues with clinical potential in antivirus chemotherapy. The effect of several thymidine and 2'-deoxycytidine analogue 5'-triphosphates on purified human (alpha, beta) and herpes simplex virus (types 1, 2) DNA polymerases.具有抗病毒化疗临床潜力的核苷类似物。几种胸苷和2'-脱氧胞苷类似物5'-三磷酸对纯化的人（α，β）和单纯疱疹病毒（1型、2型）DNA聚合酶的作用。
Mol Pharmacol. 1981 Sep;20(2):415-22.
3
Mechanisms of inhibition of DNA polymerases by 2'-deoxyribonucleoside 5'-triphosphate analogs.2'-脱氧核糖核苷5'-三磷酸类似物对DNA聚合酶的抑制机制
Methods Enzymol. 1995;262:202-17. doi: 10.1016/0076-6879(95)62019-2.
4
Synthesis of Pyridone-based Nucleoside Analogues as Substrates or Inhibitors of DNA Polymerases.基于吡啶酮的核苷类似物作为DNA聚合酶底物或抑制剂的合成
Nucleosides Nucleotides Nucleic Acids. 2016;35(4):163-77. doi: 10.1080/15257770.2015.1122197. Epub 2016 Feb 8.
5
Beta-L-thymidine 5'-triphosphate analogs as DNA polymerase substrates.β-L-胸苷5'-三磷酸类似物作为DNA聚合酶底物
J Biol Chem. 1992 Dec 15;267(35):25019-24.
6
An approach to random mutagenesis of DNA using mixtures of triphosphate derivatives of nucleoside analogues.一种使用核苷类似物三磷酸衍生物混合物对DNA进行随机诱变的方法。
J Mol Biol. 1996 Feb 2;255(4):589-603. doi: 10.1006/jmbi.1996.0049.
7
Elimination of band compression in sequencing gels by the use of N4-methyl-2'-deoxycytidine 5'-triphosphate.通过使用N4-甲基-2'-脱氧胞苷5'-三磷酸消除测序凝胶中的条带压缩。
Nucleic Acids Res. 1993 Jun 11;21(11):2709-14. doi: 10.1093/nar/21.11.2709.
8
Chemical synthesis of novel base pairs and their enzymatic incorporation into DNA.新型碱基对的化学合成及其酶促掺入DNA
Nucleic Acids Symp Ser. 1999(42):125-6. doi: 10.1093/nass/42.1.125.
9
Steady-state and pre-steady-state kinetic analysis of dNTP insertion opposite 8-oxo-7,8-dihydroguanine by Escherichia coli polymerases I exo- and II exo-.大肠杆菌聚合酶 I 外切酶和 II 外切酶对与 8-氧代-7,8-二氢鸟嘌呤相对的脱氧核苷三磷酸插入的稳态和预稳态动力学分析。
Biochemistry. 1996 Jul 30;35(30):9840-9. doi: 10.1021/bi960485x.
10
[Modified nucleoside-5'-triphosphates with an additional conjugated through the 2'-3'-fused ring as DNA polymerase substrates].[作为DNA聚合酶底物的、通过2'-3'-稠合环额外共轭的修饰核苷-5'-三磷酸]
Mol Biol (Mosk). 1994 Jan-Feb;28(1):113-26.
引用本文的文献
1
Discovery of Biofilm-Inhibiting Compounds to Enhance Antibiotic Effectiveness Against Infections.发现生物膜抑制化合物以增强抗生素对感染的疗效。
Pharmaceuticals (Basel). 2025 Feb 7;18(2):225. doi: 10.3390/ph18020225.
2
Comparison of pre-labelled primers and nucleotides as DNA labelling method for lateral flow detection of Legionella pneumophila amplicons.比较预标记引物和核苷酸作为 DNA 标记方法，用于军团菌肺炎亚种扩增子的侧向流动检测。
Sci Rep. 2024 Feb 29;14(1):5018. doi: 10.1038/s41598-024-55703-4.
3
Modified nucleoside triphosphates in bacterial research for and live-cell applications.用于细菌研究及活细胞应用的修饰核苷三磷酸。
RSC Chem Biol. 2020 Dec 1;1(5):333-351. doi: 10.1039/d0cb00078g. Epub 2020 Sep 14.
4
2-Thiouracil deprived of thiocarbonyl function preferentially base pairs with guanine rather than adenine in RNA and DNA duplexes.在RNA和DNA双链体中，失去硫羰基功能的2-硫尿嘧啶优先与鸟嘌呤而非腺嘌呤形成碱基对。
Nucleic Acids Res. 2015 Mar 11;43(5):2499-512. doi: 10.1093/nar/gkv109. Epub 2015 Feb 17.
5
Unnatural base pair systems toward the expansion of the genetic alphabet in the central dogma.非天然碱基对系统在中心法则中扩展遗传密码子。
Proc Jpn Acad Ser B Phys Biol Sci. 2012;88(7):345-67. doi: 10.2183/pjab.88.345.
6
Synthetic nucleotides as probes of DNA polymerase specificity.作为DNA聚合酶特异性探针的合成核苷酸。
J Nucleic Acids. 2012;2012:530963. doi: 10.1155/2012/530963. Epub 2012 Jun 7.
7
Probing minor groove hydrogen bonding interactions between RB69 DNA polymerase and DNA.探测 RB69 DNA 聚合酶与 DNA 之间的小沟氢键相互作用。
Biochemistry. 2012 May 29;51(21):4343-53. doi: 10.1021/bi300416z. Epub 2012 May 17.
8
Varied Molecular Interactions at the Active Sites of Several DNA Polymerases: Nonpolar Nucleoside Isosteres as Probes.几种DNA聚合酶活性位点处的多种分子相互作用：以非极性核苷类似物作为探针
J Am Chem Soc. 2000 Feb 16;122(6):1001-1007. doi: 10.1021/ja993464+.
9
Minor Groove Interactions between Polymerase and DNA: More Essential to Replication than Watson-Crick Hydrogen Bonds?聚合酶与DNA之间的小沟相互作用：对于复制而言，其比沃森-克里克氢键更重要？
J Am Chem Soc. 1999 Feb 14;121(10):2323-2324. doi: 10.1021/ja983502+.
10
Major groove derivatization of an unnatural base pair.非天然碱基对的大沟修饰。
Chembiochem. 2009 Sep 21;10(14):2394-400. doi: 10.1002/cbic.200900413.
本文引用的文献
1
A thymidine triphosphate shape analog lacking Watson-Crick pairing ability is replicated with high sequence selectivity.一种缺乏沃森-克里克配对能力的三磷酸胸苷形状类似物以高序列选择性进行复制。
Proc Natl Acad Sci U S A. 1997 Sep 30;94(20):10506-11. doi: 10.1073/pnas.94.20.10506.
2
Footprinting of echinomycin and actinomycin D on DNA molecules asymmetrically substituted with inosine and/or 2,6-diaminopurine.放线菌素和放线菌素D在被肌苷和/或2,6 - 二氨基嘌呤不对称取代的DNA分子上的足迹分析
Nucleic Acids Res. 1997 Apr 15;25(8):1502-10. doi: 10.1093/nar/25.8.1502.
3
Choosing the right sugar: how polymerases select a nucleotide substrate.选择合适的糖：聚合酶如何选择核苷酸底物。
Proc Natl Acad Sci U S A. 1997 Mar 4;94(5):1619-22. doi: 10.1073/pnas.94.5.1619.
4
PCR-based development of DNA substrates containing modified bases: an efficient system for investigating the role of the exocyclic groups in chemical and structural recognition by minor groove binding drugs and proteins.基于聚合酶链式反应（PCR）开发含修饰碱基的DNA底物：一种用于研究外环基团在小沟结合药物和蛋白质的化学及结构识别中作用的高效系统。
Proc Natl Acad Sci U S A. 1996 Nov 26;93(24):13623-8. doi: 10.1073/pnas.93.24.13623.
5
Sequence-selective intercalation of antitumour bis-naphthalimides into DNA. Evidence for an approach via the major groove.抗肿瘤双萘二甲酰胺对DNA的序列选择性嵌入。通过大沟途径的证据。
Eur J Biochem. 1996 Aug 15;240(1):195-208. doi: 10.1111/j.1432-1033.1996.0195h.x.
6
Structure of Taq polymerase with DNA at the polymerase active site.在聚合酶活性位点处与DNA结合的Taq聚合酶的结构。
Nature. 1996 Jul 18;382(6588):278-81. doi: 10.1038/382278a0.
7
Mechanistic implications from the structure of a catalytic fragment of Moloney murine leukemia virus reverse transcriptase.莫洛尼鼠白血病病毒逆转录酶催化片段结构的机制启示
Structure. 1995 Sep 15;3(9):879-92. doi: 10.1016/S0969-2126(01)00223-4.
8
Footprinting titration studies on the binding of echinomycin to DNA incapable of forming Hoogsteen base pairs.关于放线菌素与无法形成Hoogsteen碱基对的DNA结合的足迹滴定研究。
Biochemistry. 1993 Sep 7;32(35):9094-107. doi: 10.1021/bi00086a014.
9
The influence of the 2-amino group of guanine on DNA conformation. Uranyl and DNase I probing of inosine/diaminopurine substituted DNA.鸟嘌呤的2-氨基对DNA构象的影响。肌苷/二氨基嘌呤取代DNA的铀酰和DNase I探测。
EMBO J. 1995 May 1;14(9):2121-31. doi: 10.1002/j.1460-2075.1995.tb07204.x.
10
Transferring the purine 2-amino group from guanines to adenines in DNA changes the sequence-specific binding of antibiotics.将DNA中鸟嘌呤的嘌呤2-氨基转移至腺嘌呤会改变抗生素的序列特异性结合。
Nucleic Acids Res. 1995 Mar 25;23(6):885-92. doi: 10.1093/nar/23.6.885.
Zotero 插件