| pubmed-article:14963025 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:14963025 | lifeskim:mentions | umls-concept:C0162340 | lld:lifeskim |
| pubmed-article:14963025 | lifeskim:mentions | umls-concept:C1280500 | lld:lifeskim |
| pubmed-article:14963025 | lifeskim:mentions | umls-concept:C1521991 | lld:lifeskim |
| pubmed-article:14963025 | lifeskim:mentions | umls-concept:C0596040 | lld:lifeskim |
| pubmed-article:14963025 | lifeskim:mentions | umls-concept:C0162326 | lld:lifeskim |
| pubmed-article:14963025 | lifeskim:mentions | umls-concept:C1819601 | lld:lifeskim |
| pubmed-article:14963025 | lifeskim:mentions | umls-concept:C1522492 | lld:lifeskim |
| pubmed-article:14963025 | pubmed:issue | 18 | lld:pubmed |
| pubmed-article:14963025 | pubmed:dateCreated | 2004-4-26 | lld:pubmed |
| pubmed-article:14963025 | pubmed:abstractText | When mitoxantrone is activated by formaldehyde it can form adducts with DNA. These occur preferentially at CpG and CpA sequences and are enhanced 2-3-fold at methylated CpG sequences compared with non-methylated sites. We sought to understand the molecular factors involved in enhanced adduct formation at these methylated sites. This required, first, clarification of factors that contributed to the formation of adducts at CpG sites. For this purpose mass spectrometry of an oligonucleotide duplex (containing a single CpG adduct site) was used to confirm the presence of an additional carbon atom (derived from formaldehyde) on the drug-DNA complex. The effect of 3'-flanking sequences was revealed by electrophoretic analysis of oligonucleotide-drug adducts, and the preferred adduct-forming site was identified as 5'-CGG-3'. Radiolabeled studies of drug-DNA adducts confirmed that the site of attachment involved the exocyclic amino of guanine. Molecular modeling analysis of the relative stability of the intercalated form of mitoxantrone was consistent with observed adduct-forming potential of CG sites with varying flanking sequences. The known preference for adduct formation at methylated CG sites was confirmed by energetics calculations and shown to be due to a shift of equilibrium of the intercalated form of the drug from the major groove (at CG sites) to the minor groove (at methylated CG sites). This increases the relative amount of drug that is located adjacent to the N-2 exocyclic amino of guanine in the minor groove, where covalent linkage is facilitated. These results account for the enhanced covalent binding of mitoxantrone to methylated CG sequences and provide a molecular model of the interactions. | lld:pubmed |
| pubmed-article:14963025 | pubmed:language | eng | lld:pubmed |
| pubmed-article:14963025 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:14963025 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:14963025 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:14963025 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:14963025 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:14963025 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:14963025 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:14963025 | pubmed:month | Apr | lld:pubmed |
| pubmed-article:14963025 | pubmed:issn | 0021-9258 | lld:pubmed |
| pubmed-article:14963025 | pubmed:author | pubmed-author:IskanderMagdy... | lld:pubmed |
| pubmed-article:14963025 | pubmed:author | pubmed-author:CuttsSuzanne... | lld:pubmed |
| pubmed-article:14963025 | pubmed:author | pubmed-author:PhillipsDon... | lld:pubmed |
| pubmed-article:14963025 | pubmed:author | pubmed-author:ParkerBelinda... | lld:pubmed |
| pubmed-article:14963025 | pubmed:author | pubmed-author:BuleyTrevorT | lld:pubmed |
| pubmed-article:14963025 | pubmed:author | pubmed-author:EvisonBen JBJ | lld:pubmed |
| pubmed-article:14963025 | pubmed:author | pubmed-author:NeumannGreg... | lld:pubmed |
| pubmed-article:14963025 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:14963025 | pubmed:day | 30 | lld:pubmed |
| pubmed-article:14963025 | pubmed:volume | 279 | lld:pubmed |
| pubmed-article:14963025 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:14963025 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:14963025 | pubmed:pagination | 18814-23 | lld:pubmed |
| pubmed-article:14963025 | pubmed:dateRevised | 2006-11-15 | lld:pubmed |
| pubmed-article:14963025 | pubmed:meshHeading | pubmed-meshheading:14963025... | lld:pubmed |
| pubmed-article:14963025 | pubmed:meshHeading | pubmed-meshheading:14963025... | lld:pubmed |
| pubmed-article:14963025 | pubmed:meshHeading | pubmed-meshheading:14963025... | lld:pubmed |
| pubmed-article:14963025 | pubmed:meshHeading | pubmed-meshheading:14963025... | lld:pubmed |
| pubmed-article:14963025 | pubmed:meshHeading | pubmed-meshheading:14963025... | lld:pubmed |
| pubmed-article:14963025 | pubmed:meshHeading | pubmed-meshheading:14963025... | lld:pubmed |
| pubmed-article:14963025 | pubmed:meshHeading | pubmed-meshheading:14963025... | lld:pubmed |
| pubmed-article:14963025 | pubmed:meshHeading | pubmed-meshheading:14963025... | lld:pubmed |
| pubmed-article:14963025 | pubmed:meshHeading | pubmed-meshheading:14963025... | lld:pubmed |
| pubmed-article:14963025 | pubmed:meshHeading | pubmed-meshheading:14963025... | lld:pubmed |
| pubmed-article:14963025 | pubmed:year | 2004 | lld:pubmed |
| pubmed-article:14963025 | pubmed:articleTitle | A molecular understanding of mitoxantrone-DNA adduct formation: effect of cytosine methylation and flanking sequences. | lld:pubmed |
| pubmed-article:14963025 | pubmed:affiliation | Department of Biochemistry, La Trobe University, Victoria 3086, Australia. | lld:pubmed |
| pubmed-article:14963025 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:14963025 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
| http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:14963025 | lld:pubmed |
| http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:14963025 | lld:pubmed |
| http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:14963025 | lld:pubmed |
| http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:14963025 | lld:pubmed |
