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The structural basis for in situ activation of DNA alkylation by duocarmycin SA.
- Source :
-
Journal of molecular biology [J Mol Biol] 2000 Jul 28; Vol. 300 (5), pp. 1195-204. - Publication Year :
- 2000
-
Abstract
- Duocarmycin SA is a member of a growing class of interesting lead compounds for chemotherapy, distinguished by the manner in which they bind to and react with DNA substrates. The first three-dimensional structure of a DNA adduct of an unnatural enantiomer from this family has been determined by (1)H NMR methods. Comparison to the previously determined structure of the natural enantiomer bound in the same DNA-binding site provides unique insights into the similarities and critical distinctions producing the respective alkylation products and site selectivities. The results also support the hypothesis that the duocarmycin SA alkylation reaction is catalyzed by the binding to DNA, and provide a deeper understanding of the structural basis for this unique mode of activation.<br /> (Copyright 2000 Academic Press.)
- Subjects :
- Alkylating Agents chemistry
Alkylating Agents metabolism
Alkylation
Base Sequence
Binding Sites
DNA Adducts chemistry
Duocarmycins
Kinetics
Models, Molecular
Molecular Conformation
Nuclear Magnetic Resonance, Biomolecular
Oligodeoxyribonucleotides chemistry
Oligodeoxyribonucleotides metabolism
Pyrroles chemistry
Pyrroles metabolism
Stereoisomerism
Structure-Activity Relationship
Thermodynamics
Antibiotics, Antineoplastic chemistry
Antibiotics, Antineoplastic metabolism
DNA Adducts metabolism
Indoles
Subjects
Details
- Language :
- English
- ISSN :
- 0022-2836
- Volume :
- 300
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Journal of molecular biology
- Publication Type :
- Academic Journal
- Accession number :
- 10903864
- Full Text :
- https://doi.org/10.1006/jmbi.2000.3887