The macrocycle of leinamycin imparts hydrolytic stability to the thiol-sensing 1,2-dithiolan-3-one 1-oxide unit of the natural product

Santhosh Sivaramakrishnan; Leonid Breydo; Daekyu Sun; Kent S. Gates

doi:10.1016/j.bmcl.2012.04.003

The macrocycle of leinamycin imparts hydrolytic stability to the thiol-sensing 1,2-dithiolan-3-one 1-oxide unit of the natural product

Santhosh Sivaramakrishnan, Leonid Breydo, Daekyu Sun, Kent S. Gates

Research output: Contribution to journal › Article › peer-review

9 Scopus citations

Abstract

Reaction of cellular thiols with the 1,2-dithiolan-3-one 1-oxide moiety of leinamycin triggers the generation of DNA-damaging reactive intermediates. Studies with small, synthetic analogues of leinamycin reveal that the macrocyclic portion of the natural product imparts remarkable hydrolytic stability to the 1,2-dithiolan-3-one 1-oxide heterocycle without substantially compromising its thiol-sensing property.

Original language	English (US)
Pages (from-to)	3791-3794
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	22
Issue number	11
DOIs	https://doi.org/10.1016/j.bmcl.2012.04.003
State	Published - Jun 1 2012

Keywords

DNA cleavage
DNA damage

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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10.1016/j.bmcl.2012.04.003

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title = "The macrocycle of leinamycin imparts hydrolytic stability to the thiol-sensing 1,2-dithiolan-3-one 1-oxide unit of the natural product",

abstract = "Reaction of cellular thiols with the 1,2-dithiolan-3-one 1-oxide moiety of leinamycin triggers the generation of DNA-damaging reactive intermediates. Studies with small, synthetic analogues of leinamycin reveal that the macrocyclic portion of the natural product imparts remarkable hydrolytic stability to the 1,2-dithiolan-3-one 1-oxide heterocycle without substantially compromising its thiol-sensing property.",

keywords = "DNA cleavage, DNA damage",

author = "Santhosh Sivaramakrishnan and Leonid Breydo and Daekyu Sun and Gates, {Kent S.}",

note = "Funding Information: We are grateful to the National Institutes of Health for support of this work ( CA83925 and 119131 ). ",

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AU - Sivaramakrishnan, Santhosh

AU - Breydo, Leonid

AU - Sun, Daekyu

AU - Gates, Kent S.

N1 - Funding Information: We are grateful to the National Institutes of Health for support of this work ( CA83925 and 119131 ).

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N2 - Reaction of cellular thiols with the 1,2-dithiolan-3-one 1-oxide moiety of leinamycin triggers the generation of DNA-damaging reactive intermediates. Studies with small, synthetic analogues of leinamycin reveal that the macrocyclic portion of the natural product imparts remarkable hydrolytic stability to the 1,2-dithiolan-3-one 1-oxide heterocycle without substantially compromising its thiol-sensing property.

AB - Reaction of cellular thiols with the 1,2-dithiolan-3-one 1-oxide moiety of leinamycin triggers the generation of DNA-damaging reactive intermediates. Studies with small, synthetic analogues of leinamycin reveal that the macrocyclic portion of the natural product imparts remarkable hydrolytic stability to the 1,2-dithiolan-3-one 1-oxide heterocycle without substantially compromising its thiol-sensing property.

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KW - DNA damage

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The macrocycle of leinamycin imparts hydrolytic stability to the thiol-sensing 1,2-dithiolan-3-one 1-oxide unit of the natural product

Abstract

Keywords

ASJC Scopus subject areas

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