Synthesis and Bioactivity of Diastereomers of the Virulence Lanthipeptide Cytolysin

Subha Mukherjee; Liujie Huo; Gabrielle N. Thibodeaux; Wilfred A. Van Der Donk

doi:10.1021/acs.orglett.6b03246

Synthesis and Bioactivity of Diastereomers of the Virulence Lanthipeptide Cytolysin

Subha Mukherjee, Liujie Huo, Gabrielle N. Thibodeaux, Wilfred A. Van Der Donk

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

Abstract

Cytolysin, a two-component lanthipeptide comprising cytolysin S (CylL_S″) and cytolysin L (CylL_L″), is the only family member to exhibit lytic activity against mammalian cells in addition to synergistic antimicrobial activity. A subset of the thioether cross-links of CylL_S″ and CylL_L″ have ll stereochemistry instead of the canonical dl stereochemistry in all previously characterized lanthipeptides. The synthesis of a CylL_S″ variant with dl stereochemistry is reported. Its antimicrobial activity was found to be decreased, but not its lytic activity against red blood cells. Hence, the unusual ll stereochemistry is not responsible for the lytic activity.

Original language	English (US)
Pages (from-to)	6188-6191
Number of pages	4
Journal	Organic Letters
Volume	18
Issue number	23
DOIs	https://doi.org/10.1021/acs.orglett.6b03246
State	Published - Dec 2 2016

ASJC Scopus subject areas

Biochemistry
Physical and Theoretical Chemistry
Organic Chemistry

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10.1021/acs.orglett.6b03246

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title = "Synthesis and Bioactivity of Diastereomers of the Virulence Lanthipeptide Cytolysin",

abstract = "Cytolysin, a two-component lanthipeptide comprising cytolysin S (CylLS″) and cytolysin L (CylLL″), is the only family member to exhibit lytic activity against mammalian cells in addition to synergistic antimicrobial activity. A subset of the thioether cross-links of CylLS″ and CylLL″ have ll stereochemistry instead of the canonical dl stereochemistry in all previously characterized lanthipeptides. The synthesis of a CylLS″ variant with dl stereochemistry is reported. Its antimicrobial activity was found to be decreased, but not its lytic activity against red blood cells. Hence, the unusual ll stereochemistry is not responsible for the lytic activity.",

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AU - Mukherjee, Subha

AU - Huo, Liujie

AU - Thibodeaux, Gabrielle N.

AU - Van Der Donk, Wilfred A.

PY - 2016/12/2

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AB - Cytolysin, a two-component lanthipeptide comprising cytolysin S (CylLS″) and cytolysin L (CylLL″), is the only family member to exhibit lytic activity against mammalian cells in addition to synergistic antimicrobial activity. A subset of the thioether cross-links of CylLS″ and CylLL″ have ll stereochemistry instead of the canonical dl stereochemistry in all previously characterized lanthipeptides. The synthesis of a CylLS″ variant with dl stereochemistry is reported. Its antimicrobial activity was found to be decreased, but not its lytic activity against red blood cells. Hence, the unusual ll stereochemistry is not responsible for the lytic activity.

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Synthesis and Bioactivity of Diastereomers of the Virulence Lanthipeptide Cytolysin

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