Synthesis of and evaluation of lipid A modification by 4-substituted 4-deoxy arabinose analogs as potential inhibitors of bacterial polymyxin resistance.
Three sets of novel 4-deoxy-l-arabinose analogs were synthesized and evaluated as potential inhibitors of the bacterial resistance mechanism in which lipid A, on the outer membrane, is modified with 4-amino-4-deoxy-l-arabinose (l-Ara4N). One compound diminished the transfer of l-Ara4N onto lipid A. These results suggest that small molecules might be designed that would effect the same reversal of bacterial resistance observed in genetic knockouts.
Kline
T
T
Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA.
Trent
M S
MS
Stead
C M
CM
Lee
M S
MS
Sousa
M C
MC
Felise
H B
HB
Nguyen
H V
HV
Miller
S I
SI
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001089:Arabinose / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D001386:Azides / Q000138:chemical synthesis / Q000494:pharmacology; D004352:Drug Resistance, Microbial; D004357:Drug Synergism; D006602:Hexosyltransferases / Q000037:antagonists & inhibitors; D008050:Lipid A / Q000378:metabolism*; D011113:Polymyxins / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D001386:Azides; D008050:Lipid A; D011113:Polymyxins; D001089:Arabinose; D006602:Hexosyltransferases; C442226:L-Ara4N transferase