1,2,3-三唑键连核苷-氨基酸缀合物的设计、建模与合成及其作为潜在抗菌剂的研究
Design, Modeling and Synthesis of 1,2,3-Triazole-Linked Nucleoside-Amino Acid Conjugates as Potential Antibacterial Agents.
机构信息
Department of Chemistry, Rhodes College, 2000 North Parkway, Memphis, TN 38112, USA.
出版信息
Molecules. 2017 Oct 10;22(10):1682. doi: 10.3390/molecules22101682.
Abstract
Copper-catalyzed azide-alkyne cycloadditions (CuAAC or click chemistry) are convenient methods to easily couple various pharmacophores or bioactive molecules. A new series of 1,2,3-triazole-linked nucleoside-amino acid conjugates have been designed and synthesized in 57-76% yields using CuAAC. The azido group was introduced on the 5'-position of uridine or the acyclic analogue using the tosyl-azide exchange method and alkylated serine or proparylglycine was the alkyne. Modeling studies of the conjugates in the active site of LpxC indicate they have promise as antibacterial agents.
摘要
铜催化的叠氮-炔环加成反应（CuAAC 或点击化学）是一种方便的方法，可以轻松地将各种药效团或生物活性分子偶联在一起。通过 CuAAC，我们设计并合成了一系列新的 1,2,3-三唑连接的核苷-氨基酸缀合物，产率为 57-76%。通过 tosyl-叠氮交换法，在尿苷或无环类似物的 5'-位引入叠氮基团，而炔烃则是经过烷基化的丝氨酸或丙氨酸。在 LpxC 的活性位点对这些缀合物进行建模研究表明，它们有望成为抗菌剂。
相似文献
1
Design, Modeling and Synthesis of 1,2,3-Triazole-Linked Nucleoside-Amino Acid Conjugates as Potential Antibacterial Agents.
Molecules. 2017 Oct 10;22(10):1682. doi: 10.3390/molecules22101682.
2
A New Insight Into The Huisgen Reaction: Heterogeneous Copper Catalyzed Azide-Alkyne Cycloaddition for the Synthesis of 1,4-Disubstituted Triazole (From 2018-2023).
Chem Biodivers. 2024 Jun;21(6):e202400109. doi: 10.1002/cbdv.202400109. Epub 2024 May 22.
3
Toward analogues of MraY natural inhibitors: synthesis of 5'-triazole-substituted-aminoribosyl uridines through a Cu-catalyzed azide-alkyne cycloaddition.
J Org Chem. 2013 Oct 18;78(20):10088-105. doi: 10.1021/jo4014035. Epub 2013 Oct 7.
4
Halo-1,2,3-triazoles: Valuable Compounds to Access Biologically Relevant Molecules.
Chembiochem. 2024 May 17;25(10):e202400150. doi: 10.1002/cbic.202400150. Epub 2024 Apr 22.
5
Versatile site-specific conjugation of small molecules to siRNA using click chemistry.
J Org Chem. 2011 Mar 4;76(5):1198-211. doi: 10.1021/jo101761g. Epub 2011 Feb 7.
6
Ultrasound-assisted Cu(I)-catalyzed azide-alkyne click cycloaddition as polymer-analogous transformation in chitosan chemistry. High antibacterial and transfection activity of novel triazol betaine chitosan derivatives and their nanoparticles.
Int J Biol Macromol. 2019 Sep 15;137:592-603. doi: 10.1016/j.ijbiomac.2019.06.190. Epub 2019 Jun 25.
7
Recent advances in triazole synthesis via click chemistry and their pharmacological applications: A review.
Bioorg Med Chem Lett. 2024 Nov 1;112:129927. doi: 10.1016/j.bmcl.2024.129927. Epub 2024 Aug 15.
8
A comparison of triazole-forming bioconjugation techniques for constructing comb-shaped peptide-polymer bioconjugates.
Macromol Rapid Commun. 2011 Jan 17;32(2):203-8. doi: 10.1002/marc.201000507. Epub 2010 Nov 15.
9
Synthesis of 5-halogenated 1,2,3-triazoles under stoichiometric Cu(I)-mediated azide-alkyne cycloaddition (CuAAC or 'Click Chemistry').
Carbohydr Res. 2012 Nov 15;362:79-83. doi: 10.1016/j.carres.2012.08.014. Epub 2012 Sep 11.
10
An Entry of the Chemoselective Sulfo-Click Reaction into the Sphere of Nucleic Acids.
Org Lett. 2020 Mar 6;22(5):1914-1918. doi: 10.1021/acs.orglett.0c00265. Epub 2020 Feb 20.
引用本文的文献
1
Lepidiumuridine A: A New Natural Uridine Derivative as a Phytoestrogen Isolated from the Seeds of Willd.
Evid Based Complement Alternat Med. 2018 Sep 4;2018:2813465. doi: 10.1155/2018/2813465. eCollection 2018.
本文引用的文献
1
Synthesis and preliminary biological assay of uridine glycoconjugate derivatives containing amide and/or 1,2,3-triazole linkers.
Bioorg Chem. 2017 Jun;72:80-88. doi: 10.1016/j.bioorg.2017.03.015. Epub 2017 Mar 30.
2
Synthesis and anti-cancer activities of new sulfonamides 4-substituted-triazolyl nucleosides.
Bioorg Med Chem Lett. 2017 May 1;27(9):1989-1992. doi: 10.1016/j.bmcl.2017.03.018. Epub 2017 Mar 9.
3
Development and Applications of the Copper-Catalyzed Azide-Alkyne Cycloaddition (CuAAC) as a Bioorthogonal Reaction.
Molecules. 2016 Oct 24;21(10):1393. doi: 10.3390/molecules21101393.
4
Synthesis and Biological Evaluation of Triazolyl 13α-Estrone-Nucleoside Bioconjugates.
Molecules. 2016 Sep 10;21(9):1212. doi: 10.3390/molecules21091212.
5
Design, synthesis, anticancer, antimicrobial activities and molecular docking studies of theophylline containing acetylenes and theophylline containing 1,2,3-triazoles with variant nucleoside derivatives.
Eur J Med Chem. 2016 Nov 10;123:379-396. doi: 10.1016/j.ejmech.2016.07.024. Epub 2016 Jul 15.
6
Synthesis and in Vitro Antiproliferative Evaluation of C-13 Epimers of Triazolyl-d-Secoestrone Alcohols: The First Potent 13α-d-Secoestrone Derivative.
Molecules. 2016 May 12;21(5):611. doi: 10.3390/molecules21050611.
7
Synthesis and Bioactivity of Novel Trisubstituted Triazole Nucleosides.
Nucleosides Nucleotides Nucleic Acids. 2016;35(3):147-60. doi: 10.1080/15257770.2015.1115523. Epub 2016 Feb 8.
8
A Modular Approach to Phosphoglycosyltransferase Inhibitors Inspired by Nucleoside Antibiotics.
Chemistry. 2016 Mar 7;22(11):3856-64. doi: 10.1002/chem.201503986. Epub 2015 Dec 10.
9
Synthesis of Phospholipid-Protein Conjugates as New Antigens for Autoimmune Antibodies.
Molecules. 2015 Jun 3;20(6):10253-63. doi: 10.3390/molecules200610253.
10
5'-Methylene-triazole-substituted-aminoribosyl uridines as MraY inhibitors: synthesis, biological evaluation and molecular modeling.
Org Biomol Chem. 2015 Jul 14;13(26):7193-222. doi: 10.1039/c5ob00707k. Epub 2015 May 26.
Zotero 插件