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 ®rst three-dimensional structure of a DNA adduct of an unnatural enantiomer from this family has been determined by 1H NMR methods. Comparison to the previously determined structure of the natural enantiomer bound in the same DNAbinding 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
The Structural Basis for in Situ Activation of DNA Alkylation by Duocarmycin SA
BIFULCO, Giuseppe;
2000-01-01
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 ®rst three-dimensional structure of a DNA adduct of an unnatural enantiomer from this family has been determined by 1H NMR methods. Comparison to the previously determined structure of the natural enantiomer bound in the same DNAbinding 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 activationI documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
