Reversed and Sandwiched Analogs of Duocarmycin SA: Establishment of the Origin of the Sequence-Selective Alkylation of DNA and New Insights into the Source of Catalysis

Autor:	Bernd Bollinger, Dale L. Boger, Qing Jin, Donald L. Hertzog, Paul A. Kitos, Hui Cai, Douglas S. Johnson, Robert M. Garbaccio, Philippe Mesini
Rok vydání:	1997
Předmět:	Chemistry Stereochemistry Substituent General Chemistry Alkylation Biochemistry Catalysis DNA Alkylation chemistry.chemical_compound Colloid and Surface Chemistry Polynucleotide Amide Enantiomer Selectivity DNA
Zdroj:	Journal of the American Chemical Society. 119:4987-4998
ISSN:	1520-5126 0002-7863
DOI:	10.1021/ja9637210
Popis:	The synthesis and examination of two unique classes of duocarmycin SA analogs are described which we refer to as reversed and sandwiched analogs. Their examination established both the origin of the DNA alkylation selectivity and that both enantiomers of this class of natural products are subject to the same polynucleotide recognition features. The most beautiful demonstration of this is the complete switch in the enantiomeric alkylation selectivity of the reversed analogs which is only consistent with the noncovalent binding model and incompatible with alkylation site models of the origin of the DNA alkylation selectivity. In addition, dramatic alterations in the rates of DNA alkylation were observed among the agents and correlate with the presence or absence of an extended, rigid N2 amide substituent. This has led to the proposal of a previously unrecognized source of catalysis for the DNA alkylation reaction which was introduced in the preceding paper of this issue (J. Am. Chem. Soc. 1997, 119, 4977−4986).
Databáze:	OpenAIRE
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