Online citations, reference lists, and bibliographies.
Please confirm you are human
(Sign Up for free to never see this)
← Back to Search

3'-(1,2,3-Triazol-1-yl)-3'-deoxythymidine Analogs As Substrates For Human And Ureaplasma Parvum Thymidine Kinase For Structure-activity Investigations.

Jay Lin, V. Roy, L. Wang, Li You, L. Agrofoglio, D. Deville-Bonne, Tamara R. Mcbrayer, S. Coats, R. F. Schinazi, S. Eriksson
Published 2010 · Chemistry, Medicine

Save to my Library
Download PDF
Analyze on Scholarcy
Share
The pathogenic mycoplasma Ureaplasma parvum (Up) causes opportunistic infections and relies on salvage of nucleosides for DNA synthesis and Up thymidine kinase (UpTK) provides the necessary thymidine nucleotides. The anti-HIV compound 3 -azido-3'-deoxythymidine (AZT) is a good substrate for TK. Methods for a rapid and efficient synthesis of new 3'-alpha-[1,2,3]triazol-3'-deoxythymidine analogs from AZT under Huisgen conditions are described. Thirteen 3'-analogues were tested with human cytosolic thymidine kinase (hTK1) and UpTK. The new analogs showed higher efficiencies (K(m)/V(max) values) in all cases with UpTK than with hTK1. Still, hTK1 was preferentially inhibited by 9 out of 10 tested analogs. Structural models of UpTK and hTK1 were constructed and used to explain the kinetic results. Two different binding modes of the nucleosides within the active sites of both enzymes were suggested with one predominating in the bacterial enzyme and the other in hTK1. These results will aid future development of anti-mycoplasma nucleosides.
This paper references
10.1073/pnas.0406332102
Structures of thymidine kinase 1 of human and mycoplasmic origin
M. Welin (2004)
10.1177/095632020501600604
Synthesis and Antiviral Activities of 1,2,3-triazole Functionalized Thymidines: 1,3-dipolar Cycloaddition for Efficient Regioselective Diversity Generation
L. Zhou (2005)
10.1016/S0968-0896(00)00160-7
Pyrazolo-triazoles as light activable DNA cleaving agents.
S. Manfredini (2000)
10.1002/9783527619559
Microwaves in organic synthesis
A. Loupy (2002)
10.1128/AAC.46.12.3854-3860.2002
Antiviral Activities and Cellular Toxicities of Modified 2′,3′-Dideoxy-2′,3′-Didehydrocytidine Analogues
L. Stuyver (2002)
10.1590/S1415-47572007000200005
Purine and pyrimidine nucleotide metabolism in Mollicutes
C. V. Bizarro (2007)
10.1016/s0021-9258(18)68484-4
Regulation of human thymidine kinase during the cell cycle.
J. Sherley (1988)
10.1007/s00018-002-8511-x
Structure and function of cellular deoxyribonucleoside kinases
S. Eriksson (2002)
10.1021/cr9001462
Cu(I)-catalyzed Huisgen azide-alkyne 1,3-dipolar cycloaddition reaction in nucleoside, nucleotide, and oligonucleotide chemistry.
F. Amblard (2009)
10.1016/S1359-6446(03)02933-7
The growing impact of click chemistry on drug discovery.
H. Kolb (2003)
10.1002/1521-3773(20010601)40:11<2004::AID-ANIE2004>3.3.CO;2-X
Click Chemistry: Diverse Chemical Function from a Few Good Reactions.
H. Kolb (2001)
Antiviral Chem. Chemother
D. Haebich (1989)
10.1021/CC0498938
Combining Biginelli multicomponent and click chemistry: generation of 6-(1,2,3-triazol-1-yl)-dihydropyrimidone libraries.
Bogdan Khanetskyy (2004)
10.1021/JM00050A015
1,2,3-Triazole-[2',5'-bis-O-(tert-butyldimethylsilyl)-beta-D- ribofuranosyl]-3'-spiro-5"-(4"-amino-1",2"-oxathiole 2",2"-dioxide) (TSAO) analogues: synthesis and anti-HIV-1 activity.
R. Alvarez (1994)
10.3987/REV-02-562
1,2,3-Triazole Formation under Mild Conditions via 1,3-Dipolar Cycloaddition of Acetylenes with Azides
A. R. Katritzky (2003)
10.1128/AAC.00081-07
Deoxyribonucleoside Kinases Activate Nucleoside Antibiotics in Severely Pathogenic Bacteria
M. P. Sandrini (2007)
10.1016/J.TETLET.2003.10.033
A simple and fast procedure for efficient synthesis of β- and γ-azidoarylketones
P. N. Singh (2003)
10.1002/ANGE.19630751603
Kinetik und Mechanismus 1.3‐Dipolarer Cycloadditionen
R. Huisgen (1963)
10.1080/15257770600894469
Thymidine Kinase Diversity in Bacteria
M. P. Sandrini (2006)
10.1128/AAC.42.10.2620
An Escherichia coli System Expressing Human Deoxyribonucleoside Salvage Enzymes for Evaluation of Potential Antiproliferative Nucleoside Analogs
J. Wang (1998)
10.1515/HC.2000.6.5.421
Synthesis and Antibacterial Activity of some Heterocyclic β-Enamino Ester Derivatives with 1,2,3-triazole
Mingdong Chen, (2000)
10.1038/35037619
The complete sequence of the mucosal pathogen Ureaplasma urealyticum
John I. Glass (2000)
10.1016/j.febslet.2005.01.034
Structure of a type II thymidine kinase with bound dTTP
Markus S Birringer (2005)
10.1016/S0968-0896(03)00349-3
Synthesis of 1,2,3-triazolo-carbanucleoside analogues of ribavirin targeting an HCV in replicon.
Y. Saito (2003)
10.1007/BF01715117
Thymidine kinase: a tumor marker with prognostic value for non-Hodgkin's lymphoma and a broad range of potential clinical applications
M. Hallek (2005)
10.1046/j.1365-2958.2003.03717.x
Molecular characterization of thymidine kinase from Ureaplasma urealyticum: nucleoside analogues as potent inhibitors of mycoplasma growth
C. Carnrot (2003)
10.1111/j.1742-4658.2005.05030.x
Structure of the substrate complex of thymidine kinase from Ureaplasma urealyticum and investigations of possible drug targets for the enzyme
U. Kosińska (2005)
10.2174/1389557043403963
The role of thymidine kinases in the activation of pyrimidine nucleoside analogues.
A. Al-Madhoun (2004)
10.1021/OL034534R
Multivalent neoglycoconjugates by regiospecific cycloaddition of alkynes and azides using organic-soluble copper catalysts.
F. Pérez-Balderas (2003)
10.1073/PNAS.84.23.8239
Azidothymidine: crystal structure and possible functional role of the azido group.
A. Camerman (1987)
10.1093/JAC/DKM240
Nucleoside analogues are activated by bacterial deoxyribonucleoside kinases in a species-specific manner.
M. P. Sandrini (2007)
10.1110/ps.034199.107
Mechanisms of substrate selectivity for Bacillus anthracis thymidylate kinase
C. Carnrot (2008)
10.1002/1521-3773(20020715)41:14<2596::AID-ANIE2596>3.0.CO;2-4
A stepwise huisgen cycloaddition process: copper(I)-catalyzed regioselective "ligation" of azides and terminal alkynes.
V. Rostovtsev (2002)
Organic Chemistry in Ukrine
V. I. Markov (2005)
Antiviral Chem. Chemother
D. Haebich (1989)
10.1021/cc800061c
Triazole-modified histone deacetylase inhibitors as a rapid route to drug discovery.
T. Pirali (2008)
10.1016/j.bmc.2008.05.065
Anti-retroviral and cytostatic activity of 2',3'-dideoxyribonucleoside 3'-disulfides.
B. Gerland (2008)
10.3987/COM-89-5171
Synthesis of 3'-(1,2,3-triazol-1-yl)-3'-deoxythimidines
D. Haebich (1989)
10.18388/ABP.1996_4573
Structure-activity relationships for phosphorylation of nucleoside analogs to monophosphates by nucleoside kinases.
N. Johansson (1996)
10.1016/S0966-842X(01)01950-3
Ureaplasma urealyticum: an opportunity for combinatorial genomics.
J. D. Pollack (2001)
10.1128/CMR.18.4.757-789.2005
Mycoplasmas and Ureaplasmas as Neonatal Pathogens
K. Waites (2005)
10.1055/S-1991-26434
An efficient synthesis of 3'-azido-3'-deoxythymidine (AZT)
S. Czernecki (1991)
10.1039/B507975F
Efficient microwave-assisted synthesis of multivalent dendrimeric peptides using cycloaddition reaction (click) chemistry
D. Rijkers (2005)
10.1128/AAC.31.2.274
Antibacterial activity and mechanism of action of 3'-azido-3'-deoxythymidine (BW A509U).
L. Elwell (1987)
10.1080/15257770701501492
Study of Different Copper (I) Catalysts for the “Click Chemistry” Approach to Carbanucleosides
Julie Broggi (2007)
10.1038/89661
Structural basis for substrate specificities of cellular deoxyribonucleoside kinases
K. Johansson (2001)
10.1016/s0021-9258(18)31547-3
Diverging substrate specificity of pure human thymidine kinases 1 and 2 against antiviral dideoxynucleosides.
B. Munch-Petersen (1991)
10.1046/j.1365-2958.2001.02700.x
Novel deoxynucleoside‐phosphorylating enzymes in mycoplasmas: evidence for efficient utilization of deoxynucleosides
L. Wang (2001)
Detailed Comparison of the Protein-Ligand Docking Efficiencies of GOLD, a Commercial Package and ArgusLab, a Licensable Freeware
S. Joy (2006)
10.1002/JHET.5570260624
3′‐(1,2,3‐Triazol‐1‐yl)‐2′,3′‐dideoxythymidine and 3′‐(1,2,3‐triazol‐1‐yl)‐2′,3′‐dideoxyuridine
P. Wigerinck (2009)
10.1021/OL048341V
A microwave-assisted click chemistry synthesis of 1,4-disubstituted 1,2,3-triazoles via a copper(I)-catalyzed three-component reaction.
Prasad Appukkuttan (2004)



This paper is referenced by
10.3390/molecules171112665
Chemical Architecture and Applications of Nucleic Acid Derivatives Containing 1,2,3-Triazole Functionalities Synthesized via Click Chemistry
Tim C. Efthymiou (2012)
10.1080/15257770.2012.662611
Design, Synthesis, Antiviral, and Cytotoxic Evaluation of Novel Phosphonylated 1,2,3-Triazoles as Acyclic Nucleotide Analogues
I. Głowacka (2012)
10.1016/j.bmc.2015.02.063
SiO₂ nanoparticles as platform for delivery of 3'-triazole analogues of AZT-triphosphate into cells.
S. Vasilyeva (2015)
10.1021/jm401232v
Clicking 3'-azidothymidine into novel potent inhibitors of human immunodeficiency virus.
Venkata Ramana Sirivolu (2013)
10.1016/j.ejmech.2019.03.051
Naphthyl quinoxaline thymidine conjugate is a potent anticancer agent post UVA activation and elicits marked inhibition of tumor growth through vaccination.
Y. Yuan (2019)
10.1002/slct.202003355
Organocatalysis in the Synthesis of 1,2,3‐Triazoyl‐zidovudine Derivatives: Synthesis and Preliminary Antioxidant Activity
Carolina B. Gomes (2020)
10.1016/j.cdc.2020.100429
Synthesis and biological evaluation of triazolylnucleosides as antibacterial and anticancer agents
Ankit (2020)
10.1002/asia.201100432
Click chemistry: 1,2,3-triazoles as pharmacophores.
Sandip G. Agalave (2011)
10.1016/j.ejmech.2013.02.042
Design, synthesis, and biological evaluation of new 2'-deoxy-2'-fluoro-4'-triazole cytidine nucleosides as potent antiviral agents.
J. Wu (2013)
10.1016/j.ejmech.2010.12.017
Synthesis of new C5-(1-substituted-1,2,3-triazol-4 or 5-yl)-2'-deoxyuridines and their antiviral evaluation.
Aurélien Montagu (2011)
10.1016/j.bmc.2011.05.049
Facile fabrication of promising protein tyrosine phosphatase (PTP) inhibitor entities based on 'clicked' serine/threonine-monosaccharide hybrids.
X. He (2011)
10.1021/jo301146j
Synthesis of deuterated 1,2,3-triazoles.
H. K. Akula (2012)
10.1080/15257770.2019.1594282
Synthesis and anticancer activity of 3′-[4-fluoroaryl-(1,2,3-triazol-1-yl)]-3′-deoxythymidine analogs and their phosphoramidates
Natalia Kleczewska (2019)
10.1158/1541-7786.MCR-15-0403
Hypermutation of DPYD Deregulates Pyrimidine Metabolism and Promotes Malignant Progression
L. Edwards (2015)
10.1371/journal.pone.0052199
Design, Synthesis, and In Vitro and In Vivo Biological Studies of a 3′-Deoxythymidine Conjugate that Potentially Kills Cancer Cells Selectively
Q. Wei (2012)
10.1371/journal.pone.0070798
Phenyl 1,2,3-Triazole-Thymidine Ligands Stabilize G-Quadruplex DNA, Inhibit DNA Synthesis and Potentially Reduce Tumor Cell Proliferation over 3′-Azido Deoxythymidine
J. Mahesh Kumar (2013)
10.1109/NANO.2015.7388802
Delivery system for AZT-triphosphate analogues based on SiO2 nanoparticles
S. Vasilyeva (2015)
Semantic Scholar Logo Some data provided by SemanticScholar