Synthesis of a carbohydrate-derived hydroxamic acid inhibitor of the bacterial enzyme (LpxC) involved in lipid A biosynthesis

Xuechen Li; Taketo Uchiyama; Christian R H Raetz; Ole Hindsgaul

doi:10.1021/ol027458l

Synthesis of a carbohydrate-derived hydroxamic acid inhibitor of the bacterial enzyme (LpxC) involved in lipid A biosynthesis

Org Lett. 2003 Feb 20;5(4):539-41. doi: 10.1021/ol027458l.

Authors

Xuechen Li¹, Taketo Uchiyama, Christian R H Raetz, Ole Hindsgaul

Affiliation

¹ Department of Chemistry, University of Alberta, Edmonton, AB T6G 2G2, Canada.

PMID: 12583763
DOI: 10.1021/ol027458l

Abstract

[reaction: see text] The enzyme LpxC (UDP-3-O-[(R)-3-hydroxymyristoyl]-GlcNAc deacetylase) catalyzes the second step of lipid A biosynthesis and is essential for bacterial growth. A GlcNAc-derived hydroxamic acid inhibitor 8 of this enzyme was synthesized using two different routes. Compound 8 exhibits activity toward LpxC enzymes from a wider spectrum of bacterial species than any of the previously reported hydroxamic acid inhibitors.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

MeSH terms

Amidohydrolases / antagonists & inhibitors*
Carbohydrates / chemistry
Enzyme Inhibitors / chemical synthesis
Escherichia coli Proteins / antagonists & inhibitors
Hydroxamic Acids / chemical synthesis*
Hydroxamic Acids / pharmacology
Lipid A / antagonists & inhibitors
Lipid A / biosynthesis

Substances

Carbohydrates
Enzyme Inhibitors
Escherichia coli Proteins
Hydroxamic Acids
Lipid A
Amidohydrolases
UDP-3-O-acyl-N-acetylglucosamine deacetylase

Grants and funding

GM-51310/GM/NIGMS NIH HHS/United States