2-Thio derivatives of dUrd and 5-fluoro-dUrd and their 5'-monophosphates: synthesis, interaction with tumor thymidylate synthase, and in vitro antitumor activity

Bretner, Maria; Kulikowski, Tadeusz; Dzik, Jolanta M.; Balińska, Małgorzata; Rode, Wojciech; Shugar, David

doi:10.1021/jm00075a016

Cited by 57 publications

(23 citation statements)

References 15 publications

(29 reference statements)

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“…In contrast to S2U, in S2dU and S2T, the sugar rings preferentially adopt C2′- endo puckering, which is present in the parent dU and T nucleosides (21,37). The strength of S2T-A base pairing is virtually identical to that in a T-A system (38–40).…”

Section: Introductionmentioning

confidence: 99%

2-Thiouracil deprived of thiocarbonyl function preferentially base pairs with guanine rather than adenine in RNA and DNA duplexes

Sochacka

Szczepanowski

Cypryk

et al. 2015

Nucleic Acids Research

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2-Thiouracil-containing nucleosides are essential modified units of natural and synthetic nucleic acids. In particular, the 5-substituted-2-thiouridines (S2Us) present in tRNA play an important role in tuning the translation process through codon–anticodon interactions. The enhanced thermodynamic stability of S2U-containing RNA duplexes and the preferred S2U-A versus S2U-G base pairing are appreciated characteristics of S2U-modified molecular probes. Recently, we have demonstrated that 2-thiouridine (alone or within an RNA chain) is predominantly transformed under oxidative stress conditions to 4-pyrimidinone riboside (H2U) and not to uridine. Due to the important biological functions and various biotechnological applications for sulfur-containing nucleic acids, we compared the thermodynamic stabilities of duplexes containing desulfured products with those of 2-thiouracil-modified RNA and DNA duplexes. Differential scanning calorimetry experiments and theoretical calculations demonstrate that upon 2-thiouracil desulfuration to 4-pyrimidinone, the preferred base pairing of S2U with adenosine is lost, with preferred base pairing with guanosine observed instead. Therefore, biological processes and in vitro assays in which oxidative desulfuration of 2-thiouracil-containing components occurs may be altered. Moreover, we propose that the H2U-G base pair is a suitable model for investigation of the preferred recognition of 3′-G-ending versus A-ending codons by tRNA wobble nucleosides, which may adopt a 4-pyrimidinone-type structural motif.

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Section: Introductionmentioning

confidence: 99%

2-Thiouracil deprived of thiocarbonyl function preferentially base pairs with guanine rather than adenine in RNA and DNA duplexes

Sochacka

Szczepanowski

Cypryk

et al. 2015

Nucleic Acids Research

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“…These drugs may inhibit the normal metabolism and lower the gastrointestinal motility of human beings. In addition, it has also been found that TU and its derivatives readily incorporate into nucleic acids and thus display antivirus and antitumor activities [4][5][6]. Hence, it is important and urgent to develop a sensitive method to detect all of them.…”

Section: Introductionmentioning

confidence: 99%

Determination of thyreostatics in animal feeds by CE with electrochemical detector

et al. 2009

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A simple, rapid, reproducible and sensitive method based on CE with electrochemical detector was developed for the simultaneous determination of five thyreostatics including 2-thiouracil (TU), 6-methyl-2-thiouracil (MTU), 6-propyl-2-thiouracil (PTU), 6-phenyl-2-thiouracil (PhTU) and methimazole (TAP) in animal feeds. A home-made wall-jet electrochemical detector with a 300 microm diameter platinum-disk-working electrode was equipped at the end of separation capillary and used to detect oxidation currents of these thyreostatics. Under the optimum experimental conditions, TU, MTU, PTU, PhTU and TAP could be well separated within 15 min at the separation voltage of 16 kV in 20 mmol/L sodium borate buffer (pH 9.2). The detection limits (S/N=3) of the five thyreostatics in animal feeds were found to be 7.6 microg/kg for TAP, 25 microg/kg for PTU, 15 microg/kg for PhTU, 18 microg/kg for TU and 20 microg/kg for MTU by the developed CE with electrochemical detector method coupled with solid-phase extraction sample pretreatment technique.

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“…51 The best-known and most important compounds are the fluoropyrimidines and their nucleosides. 5,52 Of these, 5-fluorouracil is a prodrug because it is deoxyribosylated and then phosphorylated inside the cell.…”

Section: E N Z Y M E I N H I B I T O R S a Dump Analogsmentioning

confidence: 99%

Thymidylate synthase inhibition: A structure-based rationale for drug design

Costi

1998

Med. Res. Rev.

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2-Thio derivatives of dUrd and 5-fluoro-dUrd and their 5'-monophosphates: synthesis, interaction with tumor thymidylate synthase, and in vitro antitumor activity

Cited by 57 publications

References 15 publications

2-Thiouracil deprived of thiocarbonyl function preferentially base pairs with guanine rather than adenine in RNA and DNA duplexes

2-Thiouracil deprived of thiocarbonyl function preferentially base pairs with guanine rather than adenine in RNA and DNA duplexes

Determination of thyreostatics in animal feeds by CE with electrochemical detector

Thymidylate synthase inhibition: A structure-based rationale for drug design

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