59495-22-6Relevant academic research and scientific papers
Cytotoxic and mutagenic properties of O4-alkylthymidine lesions in Escherichia colicells
Wang, Pengcheng,Amato, Nicholas J.,Zhai, Qianqian,Wang, Yinsheng
, p. 10795 - 10803 (2016/05/09)
Due to the abundant presence of alkylating agents in living cells and the environment, DNA alkylation is generally unavoidable. Among the alkylated DNA lesions, O4-alkylthymidine (O4-alkyldT) are known to be highly mutagenic and persistent in mammalian tissues. Not much is known about how the structures of the alkyl group affect the repair and replicative bypass of the O4-alkyldT lesions, or how the latter process is modulated by translesion synthesis polymerases. Herein, we synthesized oligodeoxyribonucleotides harboring eight site-specifically inserted O4-alkyldT lesions and examined their impact on DNA replication in Escherichia colicells. We showed that the replication past all the O4-alkyldT lesions except (S)- and (R)-sBudT was highly efficient, and these lesions directed very high frequencies of dGMP misincorporation in E. coli cells. While SOS-induced DNA polymerases play redundant roles in bypassing most of theO4-alkyldT lesions, the bypass of (S)- and (R)-sBudT necessitated Pol V. Moreover, Ada was not involved in the repair of any O4-alkyldT lesions, Ogt was able to repair O4-MedT and, to a lesser extent, O4-EtdT and O4-nPrdT, but not other O4-alkyldT lesions. Together, our study provided important new knowledge about the repair of the O4-alkyldT lesions and their recognition by the E. coli replication machinery.
Solid-phase synthesis of oligonucleotides containing 4-alkoxythymidine residues
Roelen, H. C. P. F.,Brugghe, H. F.,Elst, H. van den,Marel, G. A. van der,Boom, J. H. van
, p. 99 - 104 (2007/10/02)
Immobilized and fully protected oligodeoxynucleotides containing a 4-(1,2,4-triazolyl)thymidine residue at a predetermined position were prepared according to a well-established phosphite triester methodology using 2-cyanoethyl phosphoramidites of a 4-(1,2,4-triazolyl)-substituted thymidine and standard protected nucleosides.Treatment of the immobilized oligomer with methanol, ethanol or n-propanol in the presence of DBU at 50 deg C gave the corresponding oligonucleotides containing 4-methoxy, 4-ethoxy or 4-n-propoxythymidine residue.
Carcinogenic alkylation of nucleic acid bases. Solid state and solution studies of O2-isopropyl-2-deoxythymidine
Sadana, Krishan L.,Razi, M. Tahir,Lee, Terry,Sebastian, Rudy,Buchko, Garry W.,Hruska, Frank E.
, p. 1628 - 1634 (2007/10/02)
O2-Isopropyl-2'-deoxythymidine (i2dT) crystalizes in the tetragonal space group P43212, and the cell dimension are a=b=8.7667(2), c=37,1943(12) Angstroem.X-ray intensity data were measured with a diffractometer, and the structure was solved by direct methods.Least-squares refinement, which included all hydrogen atoms, converged at R=0.036 for 1780 observed reflections.In analogy with order O-alkylated base, the exocyclic O2-C8 bond is syn-periplanar to the C2-N3 bond in the pyrimidine ring.Angular distortions in the base can be correlated with those observed in O4-alkylated pyrimidynes and O6-alkylated guanines.The conformation of the glycosyl bond is anti with κCN = 27.1 deg.The furanose ring adopts a C2' endo pucker and the conformation about C4'-C5' is gauche+. 1H nmr data show that these conformations are also preferred in solution.
Carcinogenic Alkylation of Nucleic Acid Bases. Structure and Conformation of O4-Ethyl-2'-deoxythymidine in the Solid State and in Solution
Birnbaum, George I.,Sadana, Krishan L.,Blonski, Wayne J. P.,Hruska, Frank E.
, p. 1671 - 1675 (2007/10/02)
O4-Ethyl-2'-deoxythymidine (e4dT) crystallizes in the monoclinic space group P21, and the cell dimensions are a = 5.079(1) Angstroem, b = 15.054(1) Angstroem, c = 8.467(1) Angstroem, β = 94.07(1) deg.X-ray intensity data were measured with a diffractometer, and the structure was solved by direct methods.Least-squares refinement, which included all hydrogen atoms; converged at R = 0.030 for 1365 observed reflections.The O-ethyl group is coplanar with the pyrimidine ring, the methylene carbon atom being syn to N3.It is shown that O4-alkylation causes significant changes in the geometry of the ring which can be attributed to an altered electronic structure.The conformation about the glycosidic bond is anti with χCN = 22.8 deg.The deoxyribose ring dopts the unusual C3' endo/C2' exo twist pucker, and the gauche(1+) rotamer of the CH2OH side chain is stabilized by an intramolecular C6-H...O5' hydrogen bond.Proton NMR data for e4dT and e4dU reveal the usual preference for the C2' endo sugar pucker and a conformer distribution for the C4'-C5' bond which is expected for 2'-deoxyribosides.Comments are made on the relevance of the structure to base mispairing of O-alkyl pyrimidines and their enzymatic repair.
