Five Nc-Methyladenines: Their Chemistry, Physicochemical Properties, and Biological Activities

Fujii, Tozo; Itaya, Taisuke

doi:10.3987/rev-98-500

Cited by 48 publications

(17 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The S N 2 type methylating agents such as MMS and methyl halides can react with single-stranded DNA (ssDNA) to generate large portions of N 1 -methyladenine and N 3 -methylcytosine (Figure ). ,,, These two positions are protected by hydrogen bonding in dsDNA but are quite nucleophilic when exposed in ssDNA or replication forks. When these sites are exposed, they are vulnerable to nucleophilic attack; the p K a 's of these two nitrogen sites are 4.1 and 4.5 in ssDNA, which are higher than that of N 7 -guanine. − The resulting lesions prevent formation of Watson−Crick base pairs which could be toxic for cells. The protein involved in the repair of these lesions has been revealed only very recently.…”

Section: 11 Alkylation Of Dnamentioning

confidence: 99%

Direct Reversal of DNA Alkylation Damage

2006

View full text Add to dashboard Cite

Introduction Overview of Direct Repair of DNA Alkylation DamageCellular DNA is constantly subjected to modifications by intracellular and extracellular chemicals, which can result in covalent changes. 1,2 Alkylating agents are one group of such chemicals that can lead to DNA damage. 3 These agents are prevalent in the environment and are used as anticancer compounds in the clinical setting. 4-10 Alkylating agents also exist endogenously inside cells; for instance, S-adenosylmethionine, a methyl donor for many cellular reactions, has been shown to produce methylation damage. 11,12 The attack on DNA by these alkylating agents can lead to various types of lesions on the heterocyclic bases or backbone. 3,13-15 Most of these resulting adducts are mutagenic or toxic, and cells have evolved various proteins to detect and repair them. 9,16,17 Interestingly, many of these alkylation lesions are repaired through the direct removal of the adduct. Other than the photolyase that catalyzes direct reversal of the thymine dimer created by UV light, 18,19 all known direct DNA repair proteins are engaged in alkylation DNA damage repair. These are the N-terminal domain of the Escherichia coli (E. coli) Ada protein, the O 6 -alkylguanine-DNA alkyltransferase family, and the AlkB family. 9 1.1.1. Alkylation of DNA-Alkylating reagents can be divided into S N 1 and S N 2 types based on the mechanism of the alkylation attack. The alkylation susceptibility of each site on the bases or backbone varies depending on the reagent used (Figure 1); the resulting lesions also have different mutagenic and cytotoxic effects. The N 7 -position of guanine is the most vulnerable site on DNA; unsurprisingly, it also serves as the best ligand on the DNA for metal ions such as platinum(II). 20 Treating double-stranded DNA (dsDNA) with methylating agents such as methylmethane sulfonate (MMS, an S N 2 type methylating agent) or N-methyl-N′nitrosourea (MNU, an S N 1 type methylating agent) typically results in 70-80% of the methylation occurring on the N 7 -position of guanine. Despite being the most abundant product of alkylation damage, N 7 -methylguanine is relatively innocuous and is removed mostly through spontaneous depurination. 21 The resulting abasic site is toxic and repaired enzymatically. 22 The N 3 -methyladenine is the second most abundant alkylation lesion formed in dsDNA. This lesion can block DNA replication and is removed by AlkA in E. coli and 3methyladenine-DNA-glycosylases. [23][24][25] The S N 1 type methylating agents such as MNU and N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) are highly mutagenic because they attack the oxygen atoms on DNA bases to give a significant amount of O 6 -methylguanine (O 6 -meG) and a small amount of O 4 -methylthymine (Figure 1). 13,14 O 6 -meG mispairs with thymine during DNA replication, which gives rise to a transition mutation of G:C to A:T. 26-29 Thus, this lesion must be rapidly located and removed in order to maintain the integrity of the genome. The O 6 -alkylguanine-DNA alkyltransferase family o...

show abstract

Section: 11 Alkylation Of Dnamentioning

confidence: 99%

Direct Reversal of DNA Alkylation Damage

2006

View full text Add to dashboard Cite

show abstract

“…When these sites are exposed, they are vulnerable to nucleophilic attack; the pK a 's of these two nitrogen sites are 4.1 and 4.5 in ssDNA, which are higher than that of N 7 -guanine. [34][35][36][37][38] The resulting lesions prevent formation of Watson-Crick base pairs which could be toxic for cells. The protein involved in the repair of these lesions has been revealed only very recently.…”

mentioning

confidence: 99%

Direct Reversal of DNA Alkylation Damage

Mishina

Duguid

2006

ChemInform

View full text Add to dashboard Cite

show abstract

“…The compound 3 was identified as 3-methyladenine by comparison of its EIMS, UV and NMR spectra with those reported in the literature [9,10]. 3-Methyladenine has been reported from marine organisms only once, from the sponge Topsentia genitrix [11].…”

mentioning

confidence: 85%

“…The compound 3 was identified as 3-methyladenine by comparison of its EIMS, UV and NMR spectra with those reported in the literature [9,10].…”

mentioning

confidence: 87%

8-Oxoadenine, 9-Methyl-8-Oxoadenine, and Trihydroxylated Sterols from a Far Eastern Thorectidae Sponge

Makarieva

Guzii

Dmitrenok

et al. 2006

Natural Product Communications

View full text Add to dashboard Cite

8-Oxoadenine (1) was found as a main secondary metabolite of a far-eastern Thorectidae sponge. In addition, a related minor compound, 9-methyl-8-oxoadenine (2), was isolated for the first time as a natural product, along with the previously known 3-methyladenine (3). Two known trihydroxylated sterols of the Δ 7 series (4, 5) were also identified. Structural identification of 1-5 was carried out by analysis of spectroscopic data.

show abstract

Five Nc-Methyladenines: Their Chemistry, Physicochemical Properties, and Biological Activities

Cited by 48 publications

References 0 publications

Direct Reversal of DNA Alkylation Damage

Direct Reversal of DNA Alkylation Damage

Direct Reversal of DNA Alkylation Damage

8-Oxoadenine, 9-Methyl-8-Oxoadenine, and Trihydroxylated Sterols from a Far Eastern Thorectidae Sponge

Contact Info

Product

Resources

About