- Synthesis of 8-oxo-dGTP and its β,γ-CH2-, β,γ-CHF-, and β,γ-CF2- analogues
-
Three novel bisphosphonate analogues of 8-oxo-dGTP 3 in which the bridging β,γ-oxygen is replaced by a methylene, fluoromethylene or difluoromethylene group (4–6, respectively) have been synthesized from 8-oxo-dGMP 2 by reaction of its morpholine 5′-phosphoramidate 14 or preferably, its N-methylimidazole 5′-phosphoramidate 15 with tri-n-butylammonium salts of the appropriate bisphosphonic acids, 11–13. The latter method also provides a convenient new route to 3. Analogues 4–6 may be useful as mechanistic probes for the role of 3 in abnormal DNA replication and repair.
- Zheng, Yiying,Haratipour, Pouya,Kashemirov, Boris A.,McKenna, Charles E.
-
supporting information
(2021/02/22)
-
- Synthesis of N 2-Alkyl-8-oxo-7,8-dihydro-2′-deoxyguanosine derivatives and effects of these modifications on RNA duplex stability
-
N2-Alkyl analogues of 8-oxo-7,8-dihydro-2′-deoxyguanosine (OG) were synthesized (alkyl = propyl, benzyl) via reductive amination of the protected OG nucleoside and incorporated into various positions of an RNA strand. Thermal stability studies of duplexes containing A or C opposite a single modified base revealed only moderate destabilization. Both OG as well as its N2-alkyl analogues can pair opposite A or C with nearly equal stability, potentially offering a new means of modulating RNA-protein interactions in the minor vs major grooves.
- Kannan, Arunkumar,Burrows, Cynthia J.
-
supporting information; experimental part
p. 720 - 723
(2011/03/20)
-
- Methods of screening for nucleoside analogs that are incorporated by HIV reverse transcriptase and cause incorrect base pairing
-
Methods and compositions related to HIV are disclosed. Using the methods of the present invention, nucleoside analogs may be screened for the ability to be incorporated by reverse transcriptase of human immunodeficiency virus ("HIV RT") and cause incorrec
- -
-
-
- Efficient synthesis of 8-oxo-dGTP: A mutagenic nucleotide
-
An efficient synthesis of mutagenic and oxidative DNA damage product, 8-oxo-dGTP (4) has been achieved in high yield, along with a serendipitous generation of 8-dimsyl-dG (2). In combination with dPTP (5), 8-oxo-dGTP (4) can be formulated into a kit for investigating DNA random mutagenesis. (C) 2000 Elsevier Science Ltd. All rights reserved.
- Nampalli, Satyam,Kumar, Shiv
-
p. 1677 - 1679
(2007/10/03)
-
- A serendipitous synthesis of 8-dimsyl-2′-deoxyguanosine
-
A serendipitous synthesis of 8-dimsyl-dG (2) has been achieved along with the known 8-benzyloxy-dG (3) in a nucleophilic substitution reaction of 8-bromo-dG (1) with in situ generated dimsyl and benzyloxy sodium. Compound 3 was directly converted into the
- Nampalli, Satyam,Livshin, Inna,Kumar, Shiv
-
p. 697 - 699
(2007/10/03)
-
- Synthesis of 8-oxo-7,8-dihydro-6-O-methyl-2′-deoxyguanosine and its use as a probe to study DNA-base excision by mutY enzyme
-
A 23mer oligomer containing 8-oxo-7,8-dihydro-6-O-methyl-2′-deoxyguanosine (1) has been synthesized from 2′-deoxyguanosine. The activity of MutY protein toward this and a related oligomer containing 8-methoxy-dG has been studied.
- Varaprasad, Chamakura V.,Bulychev, Nickolai,Grollman, Arthur P.,Johnson, Francis
-
-
- Mechanistic studies of the inhibition of MutT dGTPase by the carcinogenic metal Ni(II)
-
Promutagenic 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-exo-dG) levels are increased in DNA of animals exposed to carcinogenic metals, such as Ni(II). Besides being generated directly in genomic DNA, 8-oxo-dG may be incorporated there from 8-oxo-7, 8-dihydro-2'-deoxyguanosine 5'-triphosphate (8-oxo- dGTP), a product of oxidative damage to the nucleotide pool. The Escherichia coli dGTPase MutT, and analogous dGTPases in rats and humans, have been suggested as a defense against such incorporation because they hydrolyze 8- oxo-dGTP to 8-oxo-7, 8-dihydro-2'-deoxyguanosine 5'-monophosphate (8-oxo- dGMP). MutT and its mammalian counterparts are Mg(II)-dependent enzymes. Ni(II), in turn, is known to interact antagonistically with Mg(II) in biological systems. Thus, we hypothesized that Ni(II) might inhibit the activity of MutT. As an initial examination of this hypothesis, we conducted enzyme kinetic studies of MutT to determine the effect of Ni(II) on MutT activity and the mechanisms involved. As found, Ni(II) inhibited Mutt in a concentration-dependent manner when either dGTP or 8-oxo-dGTP was the nucleotide substrate. Ni(II) was determined to be an uncompetitive inhibitor of MutT with respect to Mg(II) when dGTP was the substrate, with apparent K(i) of 1.2 mM Ni(II), and a noncompetitive inhibitor with respect to Mg(II) when 8-oxo-dGTP was the substrate, with apparent K(i) of 0.9 mM Ni(II). Hence, the two metal cations did not compete with each other for binding at the Mutt active site. This makes it difficult to predict Ni(II) effects on 8- oxo-dGTPases of other species. However, based upon the amino acid sequences of human and rat MutT-like dGTPases, their capacity for Ni(II) binding should be greater than that of MutT. Whether this could lead to stronger inhibition of those enzymes by Ni(II), or not, remains to be investigated.
- Porter, Dale W.,Nelson, Victor C.,Fivash Jr., Matthew J.,Kasprzak, Kazimierz S.
-
p. 1375 - 1381
(2007/10/03)
-
- 8-Substituted guanosine and 2'-deoxyguanosine derivatives as potential inducers of the differentiation of Friend erythroleukemia cells
-
A variety of 8-substituted guanosine and 2'-deoxyguanosine derivatives were synthesized and tested as inducers of the differentiation of Friend murine erythroleukemia cells in culture. The most active agents in the guanosine series were 8-substituted -N(CH3)2, -NHCH3, -NH2, -OH, and -SO2CH3, which caused 68, 42, 34, 33, and 30% of erythroleukemia cells to attain benzidine positivity, a functional measure of maturation, at concentrations of 5, 1, 0.4, 5, and 5 mM, respectively. The 8-OH derivative of the 2'-deoxyguanosine series produced comparable activity, causing 62% benzidine-positive cells at a level of 0.2 mM. These findings indicate that 8-substituted analogues of guanosine and 2'-deoxyguanosine have the potential to terminate leukemia cell proliferation through conversion to end-stage differentiated cells.
- Lin,Cheng,Ishiguro,Sartorelli
-
p. 1194 - 1198
(2007/10/02)
-