Biomaterial Database

DNA-DNA interstrand cross-linking by 2,5-bis(1-aziridinyl)-3,6-bis(carbethoxyamino)-1,4-benzoquinone: covalent structure of the dG-to-dG cross-links in calf thymus DNA and a synthetic DNA duplex. 1994

S C Alley, and P B Hopkins

Department of Chemistry, University of Washington, Seattle 98195.

The products of the alkylation reaction of reduced 2,5-bis(1-aziridinyl)-3,6-bis(carbethoxyamino)-1,4-benzoquinone (AZQ, 1a) with duplex DNA were studied using calf thymus DNA and a synthetic oligodeoxynucleotide. Reaction of calf thymus DNA with a mixture of AZQ and ascorbic acid followed by enzymatic digestion of the sugar phosphate backbone afforded numerous AZQ-derived products including substances identified as monoadducts of AZQ with both dG and dA (with the former in greater abundance) and two diadducts, as would be expected for intrastrand or interstrand cross-links, with one containing two dG residues per AZQ and the other one each of dG and dA (with the former adduct in greater abundance). The nucleotide connectivity and covalent structure of the dG-to-dG interstrand cross-links were studied in greater detail using a synthetic DNA duplex containing the nucleotide sequence 5'-d(GGGCCC), where it appeared that the predominant interstrand cross-links bridged dG residues on opposite strands and were separated by two intervening base pairs [5'-d(GNNC)]. The covalent structure of this lesion was tentatively identified as 2b, in which the N7 atoms of two dG residues have been alkylated by the aziridine functions of AZQ, based upon the results of piperidine fragmentation and characterization of the enzymatic and acidic hydrolysates of the cross-linked DNA.

UI	MeSH Term	Description	Entries
D008958	Models, Molecular	Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.	Molecular Models,Model, Molecular,Molecular Model
D008969	Molecular Sequence Data	Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.	Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D010880	Piperidines	A family of hexahydropyridines.
D002417	Cattle	Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.	Beef Cow,Bos grunniens,Bos indicus,Bos indicus Cattle,Bos taurus,Cow,Cow, Domestic,Dairy Cow,Holstein Cow,Indicine Cattle,Taurine Cattle,Taurus Cattle,Yak,Zebu,Beef Cows,Bos indicus Cattles,Cattle, Bos indicus,Cattle, Indicine,Cattle, Taurine,Cattle, Taurus,Cattles, Bos indicus,Cattles, Indicine,Cattles, Taurine,Cattles, Taurus,Cow, Beef,Cow, Dairy,Cow, Holstein,Cows,Dairy Cows,Domestic Cow,Domestic Cows,Indicine Cattles,Taurine Cattles,Taurus Cattles,Yaks,Zebus
D003432	Cross-Linking Reagents	Reagents with two reactive groups, usually at opposite ends of the molecule, that are capable of reacting with and thereby forming bridges between side chains of amino acids in proteins; the locations of naturally reactive areas within proteins can thereby be identified; may also be used for other macromolecules, like glycoproteins, nucleic acids, or other.	Bifunctional Reagent,Bifunctional Reagents,Cross Linking Reagent,Crosslinking Reagent,Cross Linking Reagents,Crosslinking Reagents,Linking Reagent, Cross,Linking Reagents, Cross,Reagent, Bifunctional,Reagent, Cross Linking,Reagent, Crosslinking,Reagents, Bifunctional,Reagents, Cross Linking,Reagents, Cross-Linking,Reagents, Crosslinking
D003849	Deoxyguanosine	A nucleoside consisting of the base guanine and the sugar deoxyribose.
D004247	DNA	A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).	DNA, Double-Stranded,Deoxyribonucleic Acid,ds-DNA,DNA, Double Stranded,Double-Stranded DNA,ds DNA
D005559	Formamides	A group of amides with the general formula of R-CONH2.
D000478	Alkylation	The covalent bonding of an alkyl group to an organic compound. It can occur by a simple addition reaction or by substitution of another functional group.	Alkylations
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia