Reversibility of the duocarmycin A and SA DNA alkylation reaction

Duocarmycin A (1) and duocarmycin SA (2) constitute the parent agents of a growing class of potent antitumor antibiotics that exert their biological effects through a sequence selective minor groove alkylation of DNA. To date, the duocarmycin A adenine N3 alkylation has proven similar, albeit subtly...

Full description

Saved in:
Bibliographic Details
Published in:Journal of the American Chemical Society 1993-10, Vol.115 (21), p.9872-9873
Main Authors: Boger, Dale L, Yun, Weiya
Format: Article
Language:English
Subjects:
Antineoplastic agents
Biological and medical sciences
General aspects
Medical sciences
Pharmacology. Drug treatments
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Duocarmycin A (1) and duocarmycin SA (2) constitute the parent agents of a growing class of potent antitumor antibiotics that exert their biological effects through a sequence selective minor groove alkylation of DNA. To date, the duocarmycin A adenine N3 alkylation has proven similar, albeit subtly distinct, from that of (+)-CC-1065 (3) and structurally related analogs. Herein, we detail the reversible nature of the (+)-duocarmycin A and SA DNA alkylation reactions which complement the recent report that simplified analogs of (+)-CC-1065, but not (+)-CC-1065 itself, reversibly alkylate duplex DNA. The ramifications of these observations and the distinctions in the relative reversibility of the reactions are discussed.
ISSN:0002-7863
1520-5126
DOI:10.1021/ja00074a093