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Biochem J. 1993 Sep 1;294 ( Pt 2)(Pt 2):381-5. doi: 10.1042/bj2940381.
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引用本文的文献

1
Sensitivity of monkey B virus (Cercopithecine herpesvirus 1) to antiviral drugs: role of thymidine kinase in antiviral activities of substrate analogs and acyclonucleosides.猴B病毒（猕猴疱疹病毒1型）对抗病毒药物的敏感性：胸苷激酶在底物类似物和无环核苷抗病毒活性中的作用
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2
Molecular biology of pseudorabies virus: impact on neurovirology and veterinary medicine.伪狂犬病病毒的分子生物学：对神经病毒学和兽医学的影响。
Microbiol Mol Biol Rev. 2005 Sep;69(3):462-500. doi: 10.1128/MMBR.69.3.462-500.2005.
3
L-ATP is recognized by some cellular and viral enzymes: does chance drive enzymic enantioselectivity?L-ATP被一些细胞酶和病毒酶所识别：是偶然性驱动酶的对映体选择性吗？
Biochem J. 1999 Feb 1;337 ( Pt 3)(Pt 3):585-90.
4
Relaxed enantioselectivity of human mitochondrial thymidine kinase and chemotherapeutic uses of L-nucleoside analogues.人线粒体胸苷激酶的宽松对映选择性及L-核苷类似物的化疗用途。
Biochem J. 1997 Nov 15;328 ( Pt 1)(Pt 1):317-20. doi: 10.1042/bj3280317.

本文引用的文献

1
Synthesis and biological activities of iododeoxyuridine, an analog of thymidine.胸腺嘧啶核苷类似物碘脱氧尿苷的合成及生物活性
Biochim Biophys Acta. 1959 Mar;32(1):295-6. doi: 10.1016/0006-3002(59)90597-9.
2
Inhibition of purified human and herpes simplex virus-induced DNA polymerases by 9-(2-hydroxyethoxymethyl)guanine triphosphate. Effects on primer-template function.9-(2-羟乙氧甲基)鸟嘌呤三磷酸对纯化的人及单纯疱疹病毒诱导的DNA聚合酶的抑制作用。对引物-模板功能的影响。
J Biol Chem. 1981 Nov 25;256(22):11447-51.
3
Statistical considerations in the estimation of enzyme kinetic parameters by the direct linear plot andother methods.通过直接线性作图法及其他方法估算酶动力学参数时的统计学考量
Biochem J. 1974 Jun;139(3):721-30. doi: 10.1042/bj1390721.
4
Demonstration of viral thymidine kinase inhibitor and its effect on deoxynucleotide metabolism in cells infected with herpes simplex virus.病毒胸苷激酶抑制剂的证明及其对单纯疱疹病毒感染细胞中脱氧核苷酸代谢的影响。
Antimicrob Agents Chemother. 1987 Mar;31(3):368-74. doi: 10.1128/AAC.31.3.368.
5
Synthesis and antiviral activity of (E)-5-(2-bromovinyl)uracil and (E)-5-(2-bromovinyl)uridine.（E）-5-（2-溴乙烯基）尿嘧啶和（E）-5-（2-溴乙烯基）尿苷的合成及其抗病毒活性
J Med Chem. 1986 Feb;29(2):213-7. doi: 10.1021/jm00152a008.
6
Chemotherapy of Aujeszky's disease (pseudorabies) in the mouse by means of nucleoside analogues: bromovinyldeoxyuridine, acyclovir, and dihydroxypropoxymethylguanine.利用核苷类似物对小鼠奥耶斯基氏病（伪狂犬病）进行化学疗法：溴乙烯脱氧尿苷、阿昔洛韦和二羟基丙氧基甲基鸟嘌呤。
Antiviral Res. 1985 Jun;5(3):157-68. doi: 10.1016/0166-3542(85)90048-8.
7
Vaccination of swine with thymidine kinase-deficient mutants of pseudorabies virus.用伪狂犬病病毒胸苷激酶缺陷型突变体对猪进行疫苗接种。
Am J Vet Res. 1985 Jul;46(7):1494-7.
8
Attenuated properties of thymidine kinase-negative deletion mutant of pseudorabies virus.伪狂犬病病毒胸苷激酶阴性缺失突变体的减毒特性
Am J Vet Res. 1985 Jun;46(6):1359-67.
9
N2-phenyldeoxyguanosine: a novel selective inhibitor of herpes simplex thymidine kinase.N2-苯基脱氧鸟苷：一种新型单纯疱疹胸苷激酶选择性抑制剂。
J Med Chem. 1988 Aug;31(8):1496-500. doi: 10.1021/jm00403a004.
10
Nucleoside analogs as non-substrate inhibitors of herpes simplex viruses thymidine kinase.核苷类似物作为单纯疱疹病毒胸苷激酶的非底物抑制剂
Methods Find Exp Clin Pharmacol. 1989 Sep;11(9):577-82.

猪伪狂犬病病毒胸苷激酶缺乏立体特异性。

Lack of stereospecificity of suid pseudorabies virus thymidine kinase.

作者信息

Maga G, Verri A, Bonizzi L, Ponti W, Poli G, Garbesi A, Niccolai D, Spadari S, Focher F

机构信息

Istituto de Genetica Biochimica ed Evoluzionistica, CNR, Pavia, Italy.

出版信息

Biochem J. 1993 Sep 1;294 ( Pt 2)(Pt 2):381-5. doi: 10.1042/bj2940381.

DOI:10.1042/bj2940381
PMID:8396911
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1134465/
Abstract

We have partially purified suid pseudorabies virus (PRV) thymidine kinase from infected thymidine kinase- mouse cells, and cytosolic swine thymidine kinase from lymphatic glands, and we have found that PRV thymidine kinase, unlike the host enzyme, shows no stereospecificity for D- and L-beta-nucleosides. In vitro, unnatural L-enantiomers, except L-deoxycytidine, function as specific inhibitors for the viral enzyme in the order: L-thymidine >> L-deoxyguanosine > L-deoxyuridine > L-deoxyadenosine. Contrary to human and swine thymidine kinases and like herpes simplex virus-1 and -2 thymidine kinases, PRV thymidine kinase phosphorylates both the natural (D-) and the unnatural (L-) thymidine enantiomers to their corresponding monophosphates with comparable efficiency. The kinetic parameters Vmax/Km for D- and L-thymidine are 3.7 and 2.3 respectively. Our results demonstrate that the lack of stereospecificity might be a common feature of the thymidine kinases that are encoded by human and animal herpes viruses. These observations could lead to the development of a novel class of antiviral drugs.

摘要

我们已从感染的胸苷激酶缺陷型小鼠细胞中部分纯化了猪伪狂犬病病毒（PRV）胸苷激酶，并从淋巴腺中纯化了胞质猪胸苷激酶，且我们发现，与宿主酶不同，PRV胸苷激酶对D-和L-β-核苷没有立体特异性。在体外，除L-脱氧胞苷外，非天然L-对映体作为病毒酶的特异性抑制剂，其抑制顺序为：L-胸苷 >> L-脱氧鸟苷 > L-脱氧尿苷 > L-脱氧腺苷。与人和猪的胸苷激酶相反，与单纯疱疹病毒1型和2型胸苷激酶相似，PRV胸苷激酶能以相当的效率将天然（D-）和非天然（L-）胸苷对映体磷酸化为相应的单磷酸酯。D-和L-胸苷的动力学参数Vmax/Km分别为3.7和2.3。我们的结果表明，缺乏立体特异性可能是人和动物疱疹病毒编码的胸苷激酶的共同特征。这些观察结果可能会促成一类新型抗病毒药物的开发。