Comprehensive Analysis of DNA Strand Breaks at the Guanosine Site Induced by Low-Energy Electron Attachment

doi:10.1002/cphc.200900656

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	Comprehensive Analysis of DNA Strand Breaks at the Guanosine Site Induced by Low-Energy Electron Attachment
	Gu, Jiande1,2 ; Wang, Jing 1; Leszczynski, Jerzy 1
刊名	CHEMPHYSCHEM
	2010-01-18
卷号	11 期号:1 页码:175-181
关键词	density functional calculations DNA damage electron transfer guanosine low-energy electrons
ISSN号	1439-4235
DOI	10.1002/cphc.200900656
文献子类	Article
英文摘要	To elucidate the role of guanosine in DNA strand breaks caused by low-energy electrons (LEES), theoretical investigations of the LEE attachment-induced C-O sigma-bonds and N-glycosidic bond breaking of 2'-deoxyguanosine-3',5'-diphosphate (3',5'-dGMP) were performed using the B3LYP/DZP++ approach. The results reveal possible reaction pathways in the gas phase and in aqueous solutions. In the gas phase LEES could attach to the phosphate group adjacent to the guanosine to form a radical anion. However, the small vertical detachment energy (VDE) of the radical anion of guanosine 3',5'-diphosphate in the gas phase excludes either C-O bond cleavage or N-glycosidic bond breaking. In the presence of the polarizable surroundings, the solvent effects dramatically increase the electron affinities of the 3',5'-dGDP and the VDE of 3',5'-dGDP(-). Furthermore, the solvent-solute interactions greatly reduce the activation barriers of the C-O bond cleavage to 1.06-3.56 kcal mol(-1). These low-energy barriers ensure that either C-5-O-5. or C-3-O-3, bond rupture takes place at the guanosine site in DNA single strands. On the other hand, the comparatively high energy barrier of the N-glycosidic bond rupture implies that this reaction pathway is inferior to C-O bond cleavage. Qualitative agreement was found between the theoretical sequence of the bond breaking reaction pathways in the PCM model and the ratio for the corresponding bond breaks observed in the experiment of LEE-induced damage in oligonucleotide tetramer CGTA. This concord suggests that the influence of the surroundings in the thin solid film on the LEE-induced DNA damage resembles that of the solvent.
资助项目	NSF CREST[HRD-0833178]
WOS关键词	GLYCOSIDIC BOND-CLEAVAGE ; PYRIMIDINE NUCLEOTIDES ; AQUEOUS-SOLUTION ; DAMAGE ; SINGLE ; NUCLEOSIDES ; AFFINITIES ; THYMINE ; MODEL ; FRAGMENTS
WOS研究方向	Chemistry ; Physics
语种	英语
出版者	WILEY-V C H VERLAG GMBH
WOS记录号	WOS:000274265300024
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/278992]
专题	药物发现与设计中心中科院受体结构与功能重点实验室新药研究国家重点实验室
通讯作者	Gu, Jiande
作者单位	1.Jackson State Univ, Dept Chem, Interdisciplinary Nanotox Certer, Jackson, MS 39217 USA 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res,Shanghai Inst Biol Sci, Drug Design & Discovery Ctr, Shanghai 201203, Peoples R China;
推荐引用方式 GB/T 7714	Gu, Jiande,Wang, Jing,Leszczynski, Jerzy. Comprehensive Analysis of DNA Strand Breaks at the Guanosine Site Induced by Low-Energy Electron Attachment[J]. CHEMPHYSCHEM,2010,11(1):175-181.
APA	Gu, Jiande,Wang, Jing,&Leszczynski, Jerzy.(2010).Comprehensive Analysis of DNA Strand Breaks at the Guanosine Site Induced by Low-Energy Electron Attachment.CHEMPHYSCHEM,11(1),175-181.
MLA	Gu, Jiande,et al."Comprehensive Analysis of DNA Strand Breaks at the Guanosine Site Induced by Low-Energy Electron Attachment".CHEMPHYSCHEM 11.1(2010):175-181.