Duocarmycin
Encyclopedia
The duocarmycins are a series of related natural product
s first isolated from Streptomyces
bacteria in 1988. They were found to have potent antitumor properties.
Through the work of Dale L. Boger
and others, the pharmacophore
and mechanism of action
were elucidated. The duocarmycins bind to the minor groove of DNA and alkylate
the nucleobase adenine
at the N3 position. This research led to synthetic analogs including adozelesin, bizelesin, and carzelesin which progressed into clinical trials for the treatment of cancer.
Natural product
A natural product is a chemical compound or substance produced by a living organism - found in nature that usually has a pharmacological or biological activity for use in pharmaceutical drug discovery and drug design...
s first isolated from Streptomyces
Streptomyces
Streptomyces is the largest genus of Actinobacteria and the type genus of the family Streptomycetaceae. Over 500 species of Streptomyces bacteria have been described. As with the other Actinobacteria, streptomycetes are gram-positive, and have genomes with high guanine and cytosine content...
bacteria in 1988. They were found to have potent antitumor properties.
Through the work of Dale L. Boger
Dale L. Boger
Dale Lester Boger is an American medicinal and organic chemist. Dale Boger was born on August 22, 1953, in Hutchinson, Kansas. He studied chemistry at the University of Kansas , Ph.D. 1980, Harvard University, under Professor E. J. Corey...
and others, the pharmacophore
Pharmacophore
thumb|right|300px|An example of a pharmacophore model.A pharmacophore is an abstract description of molecular features which are necessary for molecular recognition of a ligand by a biological macromolecule....
and mechanism of action
Mechanism of action
In pharmacology, the term mechanism of action refers to the specific biochemical interaction through which a drug substance produces its pharmacological effect...
were elucidated. The duocarmycins bind to the minor groove of DNA and alkylate
Alkylation
Alkylation is the transfer of an alkyl group from one molecule to another. The alkyl group may be transferred as an alkyl carbocation, a free radical, a carbanion or a carbene . Alkylating agents are widely used in chemistry because the alkyl group is probably the most common group encountered in...
the nucleobase adenine
Adenine
Adenine is a nucleobase with a variety of roles in biochemistry including cellular respiration, in the form of both the energy-rich adenosine triphosphate and the cofactors nicotinamide adenine dinucleotide and flavin adenine dinucleotide , and protein synthesis, as a chemical component of DNA...
at the N3 position. This research led to synthetic analogs including adozelesin, bizelesin, and carzelesin which progressed into clinical trials for the treatment of cancer.