Methylation of Thiouracils and Thioxanthines with Trimethyl Phosphate

Hayashi, Masahiro; Hisanaga, Yorisato; Yamauchi, Kiyoshi; Kinoshita, Masayoshi

doi:10.1080/00397918008061843

Cited by 5 publications

(1 citation statement)

References 6 publications

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“…Base analogs (see Fig. 1 compounds: 2-18) were obtained according to previously described procedures: compounds 2, 3, 9 (Beaman, 1954); 4, 12 (Bendich et al, 1948); 5 (Yamazaki et al, 1968); 6 (Lichtenberg et al, 1972); 7 (Hayashi et al, 1980); 8 (Kazimierczuk & Shugar, 1974); 10, 11 (Taylor & Chain, 1952); 13 (Papesch & Schroeder, 1951); 14, 15 (Kazimierczuk et al, 1972); 16 (Traube, 1904); 17 (Pfleiderer & Fink, 1962); 18 (Huebsch & Pfleiderer, 1988). The purity of the compounds was ascertained by TLC, UV, and mass spectra analysis (not shown).…”

Section: Reagentsmentioning

confidence: 99%

Inhibition of DNA repair glycosylases by base analogs and tryptophan pyrolysate, Trp-P-1.

Speina

Cieśla²,

Gra̧ziewicz³

et al. 2005

Acta Biochim Pol

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DNA base analogs, 2,4,5,6-substituted pyrimidines and 2,6-substituted purines were tested as potential inhibitors of E. coli Fpg protein (formamidopyrimidine -DNA glycosylase). Three of the seventeen compounds tested revealed inhibitory properties. 2-Thioxanthine was the most efficient, inhibiting 50% of 2,6-diamino-4-hydroxy-5N-methyl-formamidopyrimidine (Fapy-7MeG) excision activity at 17.1 mM concentration. The measured K i was 4.44 ± 0.15 mM. Inhibition was observed only when the Fpg protein was first challenged to its substrate followed by the addition of the base analog, suggesting uncompetitive (catalytic) inhibition. For two other com-Vol. 52 No. 1/2005 167-178 QUARTERLY . ; [ 3 H]MNU-DNA, DNA alkylated with [ 3 H]methylnitrosourea; 8-oxoG, 8-oxoguanine; Trp-P-1, 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole. pounds, 2-thio-or 2-oxo-4,5,6-substituted pyrimidines, IC 50 was only 343.3 ± 58.6 and 350 ± 24.4 mM, respectively. No change of the Fpg glycosylase activity was detected in the presence of Fapy-7MeG, up to 5 mM. We also investigated the effect of DNA structure modified by tryptophan pyrolysate (Trp-P-1) on the activity of base excision repair enzymes: Escherichia coli and human DNA glycosylases of oxidized (Fpg, Nth) and alkylated bases (TagA, AlkA, and ANPG), and for bacterial AP endonuclease (Xth protein). Trp-P-1, which changes the secondary DNA structure into non-B, non-Z most efficiently inhibited excision of alkylated bases by the AlkA glycosylase (IC 50 = 1 mM). The ANPG, TagA, and Fpg proteins were also inhibited although to a lesser extent (IC 50 = 76.5 mM, 96 mM, and 187.5 mM, respectively). Trp-P-1 also inhibited incision of DNA at abasic sites by the b-lyase activity of the Fpg and Nth proteins, and to a lesser extent by the Xth AP endonuclease. Thus, DNA conformation is critical for excision of damaged bases and incision of abasic sites by DNA repair enzymes.

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Section: Reagentsmentioning

confidence: 99%

Inhibition of DNA repair glycosylases by base analogs and tryptophan pyrolysate, Trp-P-1.

Speina

Cieśla²,

Gra̧ziewicz³

et al. 2005

Acta Biochim Pol

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ChemInform Abstract: METHYLATION OF THIOURACILS AND THIOXANTHINES WITH TRIMETHYL PHOSPHATE

HAYASHI¹,

Hisanaga²,

Yamauchi³

et al. 1981

Chemischer Informationsdienst

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Reactions of 6‐thiotheophylline with alkylating agents and epichlorohydrin: Isolation of S‐alkylated 6‐thiotheophylline and 7‐(2,3‐thioepoxypropyl)theophylline

Hayashi

Suzuki

Yasuzawa

et al. 1993

Journal of Heterocyclic Chem

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Alkylation of 6‐thiotheophylline (1) under the aprotic basic condition affords S‐alkylated 6‐thiotheophylline (3) together with an N7 ‐alkylated product 4. There is a tendency that the more reactive the alkylating agents are, the higher the yields of S‐alkylated products are. On the other hand, treatment of 6‐thiotheophylline (1) with epichlorohydrin afforded an unexpected product, 7‐(2,3‐thioepoxypropyl)theophylline (6), neither an S‐alkylated compound 3g nor an N7 ‐alkylated compound 4g. The chemical structure was determined by nmr spectroscopic analysis.

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Methylation of Thiouracils and Thioxanthines with Trimethyl Phosphate

Cited by 5 publications

References 6 publications

Inhibition of DNA repair glycosylases by base analogs and tryptophan pyrolysate, Trp-P-1.

Inhibition of DNA repair glycosylases by base analogs and tryptophan pyrolysate, Trp-P-1.

ChemInform Abstract: METHYLATION OF THIOURACILS AND THIOXANTHINES WITH TRIMETHYL PHOSPHATE

Reactions of 6‐thiotheophylline with alkylating agents and epichlorohydrin: Isolation of S‐alkylated 6‐thiotheophylline and 7‐(2,3‐thioepoxypropyl)theophylline

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