Probing DNA bulges with designed helical spirocyclic molecules.

Probing DNA bulges with designed helical spirocyclic molecules. Research Abstract Details 

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Probing DNA bulges with designed helical spirocyclic molecules. Abstract Text:

Lizzy S Kappen,Yiqing Lin,Graham B Jones,Irving H Goldberg,

Because bulged structures (unpaired bases) in nucleic acids are of general biological significance, it has been of interest to design small molecules as specific probes of bulge function. On the basis of our earlier work with the specific DNA bulge-binding metabolite obtained from the enediyne antitumor antibiotic neocarzinostatin chromophore (NCS-chrom), we have prepared three small helical spirocyclic molecules that most closely mimic the natural product. These wedge-shaped molecules resemble the natural product in having the sugar residue attached to the same five-membered ring system. In one instance, the sugar is aminoglucose in beta-glycosidic linkage, and in the other, two enantiomers have the natural sugar N-methylfucosamine in alpha-glycosidic linkage. All three analogues were found to interfere with bulge-specific cleavage by NCS-chrom and the ability of bulged DNA to serve as a template for DNA polymerase 1 in accordance with their binding affinities for DNA containing a two-base bulge. Comparable results were obtained with the analogues for the less efficiently cleaved three-base bulge DNA structures. In each situation, the enantiomers possessing the natural sugar in alpha-glycosidic linkage are the most potent inhibitors of the cleavage reaction. In the DNA polymerase reactions, again, the closest natural product mimics were the most effective in selectively impeding nucleotide extension at the bulge site, presumably by complex formation. These results demonstrate the potential usefulness of bulge-binding compounds in modifying DNA structure and function and support efforts to design and prepare reactive species of these molecules that can covalently modify bulged DNA.

Probing DNA bulges with designed helical spirocyclic molecules. Publishing Authors By Initials

LS Kappen,Y Lin,GB Jones,IH Goldberg,

For similar organic chemicals: hydrocarbons: hydrocarbons, cyclic: hydrocarbons, aromatic: polycyclic hydrocarbons, aromatic: spiro compounds research abstracts see: organic chemicals: hydrocarbons: hydrocarbons, cyclic: hydrocarbons, aromatic: polycyclic hydrocarbons, aromatic: spiro compounds research

PUBMED ID PMID:

MEDLINE DATE:

Probing DNA bulges with designed helical spirocyclic molecules. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Biochemistry

VOLUME: 46

Page Numbers: 561-7

Journal Abbreviation: Biochemistry

ISSN: 0006-2960

DAY: 16

MONTH: Jan

YEAR: 2007

Probing DNA bulges with designed helical spirocyclic molecules. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 370623

Probing DNA bulges with designed helical spirocyclic molecules. Keywords Mesh Terms:

KEYWORDS: Spiro Compounds

MESH TERMS: chemistry

Chemical & Substance for Abstract: Probing DNA bulges with designed helical spirocyclic molecules. Information

Substance Name: DNA

Registry Number: 9007-49-2

Grant and Affiliation Information for Probing DNA bulges with designed helical spirocyclic molecules.

AFFILIATION: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA.

Country: United States

AGENCY: United States NIGMS

GRANT: GM 53793

ACRONYM: GM

MEDLINETA: Biochemistry

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