The structural basis for in situ activation of DNA alkylation by duocarmycin SA.

Smith JA, Bifulco G, Case DA, Boger DL, Gomez-Paloma L, Chazin WJ
J Mol Biol. 2000 300 (5): 1195-204

PMID: 10903864 · DOI:10.1006/jmbi.2000.3887

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.

Copyright 2000 Academic Press.

MeSH Terms (17)

Alkylating Agents Alkylation Antibiotics, Antineoplastic Base Sequence Binding Sites DNA Adducts Duocarmycins Indoles Kinetics Models, Molecular Molecular Conformation Nuclear Magnetic Resonance, Biomolecular Oligodeoxyribonucleotides Pyrroles Stereoisomerism Structure-Activity Relationship Thermodynamics

Connections (1)

This publication is referenced by other Labnodes entities: