Selective reduction of methylsulfinyl-containing compounds by mammalian MsrA suggests a strategy for improved drug efficacy

Byung Cheon Lee, Dmitri E. Fomenko, Vadim N. Gladyshev

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Identification of pathways of drug metabolism provides critical information regarding efficacy and safety of these compounds. Particularly challenging cases involve stereospecific processes. We found that broad classes of compounds containing methylsulfinyl groups are reduced to methylsulfides specifically by methionine sulfoxide reductase A, which acts on the S-stereomers of methionine sulfoxides, whereas the R-stereomers of these compounds could not be efficiently reduced by any methionine sulfoxide reductase in mammals. The findings of efficient reduction of S-methylsulfinyls and deficiency in the reduction of R-methylsulfinyls by methionine sulfoxide reductases suggest strategies for improved efficacy and decreased toxicity of drugs and natural compounds containing methylsulfinyls through targeted use of their enantiomers.

Original languageEnglish
Pages (from-to)1029-1035
Number of pages7
JournalACS Chemical Biology
Volume6
Issue number10
DOIs
Publication statusPublished - 2011 Oct 21
Externally publishedYes

Fingerprint

Methionine Sulfoxide Reductases
Mammals
Enantiomers
Drug-Related Side Effects and Adverse Reactions
Metabolism
Pharmaceutical Preparations
Toxicity
Safety

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine

Cite this

Selective reduction of methylsulfinyl-containing compounds by mammalian MsrA suggests a strategy for improved drug efficacy. / Lee, Byung Cheon; Fomenko, Dmitri E.; Gladyshev, Vadim N.

In: ACS Chemical Biology, Vol. 6, No. 10, 21.10.2011, p. 1029-1035.

Research output: Contribution to journalArticle

@article{0fa09a998ef14f76a808c8c53b7f387b,
title = "Selective reduction of methylsulfinyl-containing compounds by mammalian MsrA suggests a strategy for improved drug efficacy",
abstract = "Identification of pathways of drug metabolism provides critical information regarding efficacy and safety of these compounds. Particularly challenging cases involve stereospecific processes. We found that broad classes of compounds containing methylsulfinyl groups are reduced to methylsulfides specifically by methionine sulfoxide reductase A, which acts on the S-stereomers of methionine sulfoxides, whereas the R-stereomers of these compounds could not be efficiently reduced by any methionine sulfoxide reductase in mammals. The findings of efficient reduction of S-methylsulfinyls and deficiency in the reduction of R-methylsulfinyls by methionine sulfoxide reductases suggest strategies for improved efficacy and decreased toxicity of drugs and natural compounds containing methylsulfinyls through targeted use of their enantiomers.",
author = "Lee, {Byung Cheon} and Fomenko, {Dmitri E.} and Gladyshev, {Vadim N.}",
year = "2011",
month = "10",
day = "21",
doi = "10.1021/cb2001395",
language = "English",
volume = "6",
pages = "1029--1035",
journal = "ACS Chemical Biology",
issn = "1554-8929",
publisher = "American Chemical Society",
number = "10",

}

TY - JOUR

T1 - Selective reduction of methylsulfinyl-containing compounds by mammalian MsrA suggests a strategy for improved drug efficacy

AU - Lee, Byung Cheon

AU - Fomenko, Dmitri E.

AU - Gladyshev, Vadim N.

PY - 2011/10/21

Y1 - 2011/10/21

N2 - Identification of pathways of drug metabolism provides critical information regarding efficacy and safety of these compounds. Particularly challenging cases involve stereospecific processes. We found that broad classes of compounds containing methylsulfinyl groups are reduced to methylsulfides specifically by methionine sulfoxide reductase A, which acts on the S-stereomers of methionine sulfoxides, whereas the R-stereomers of these compounds could not be efficiently reduced by any methionine sulfoxide reductase in mammals. The findings of efficient reduction of S-methylsulfinyls and deficiency in the reduction of R-methylsulfinyls by methionine sulfoxide reductases suggest strategies for improved efficacy and decreased toxicity of drugs and natural compounds containing methylsulfinyls through targeted use of their enantiomers.

AB - Identification of pathways of drug metabolism provides critical information regarding efficacy and safety of these compounds. Particularly challenging cases involve stereospecific processes. We found that broad classes of compounds containing methylsulfinyl groups are reduced to methylsulfides specifically by methionine sulfoxide reductase A, which acts on the S-stereomers of methionine sulfoxides, whereas the R-stereomers of these compounds could not be efficiently reduced by any methionine sulfoxide reductase in mammals. The findings of efficient reduction of S-methylsulfinyls and deficiency in the reduction of R-methylsulfinyls by methionine sulfoxide reductases suggest strategies for improved efficacy and decreased toxicity of drugs and natural compounds containing methylsulfinyls through targeted use of their enantiomers.

UR - http://www.scopus.com/inward/record.url?scp=80055017121&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80055017121&partnerID=8YFLogxK

U2 - 10.1021/cb2001395

DO - 10.1021/cb2001395

M3 - Article

C2 - 21823615

AN - SCOPUS:80055017121

VL - 6

SP - 1029

EP - 1035

JO - ACS Chemical Biology

JF - ACS Chemical Biology

SN - 1554-8929

IS - 10

ER -