Antibiotic evaluation and in vivo analysis of alkynyl Coenzyme A antimetabolites in Escherichia coli.
Pantothenamides have been the subject of much study as potential inhibitors of CoA and carrier protein dependent biosynthetic pathways. Based on an initial observation of growth inhibition in Escherichia coli by 3, we have synthesized a small panel of pantetheine analogues and re-examined the inhibitory properties of this class of antibiotics with an emphasis on understanding the ability of these compounds to act as substrates of native CoA and carrier protein utilizing biosynthetic pathways. Our findings suggest that a secondary structure-activity relationship is an important factor in the antibiotic activity of these compounds.
Mercer
Andrew C
AC
Department of Chemistry and Biochemistry, University of California-San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0358, USA.
Meier
Jordan L
JL
Hur
Gene H
GH
Smith
Andrew R
AR
Burkart
Michael D
MD
D000446:Aldehyde-Lyases / Q000032:analysis / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000378:metabolism; D000963:Antimetabolites / Q000378:metabolism*; D003065:Coenzyme A / Q000378:metabolism*; D020650:Combinatorial Chemistry Techniques; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis / Q000378:metabolism; D004926:Escherichia coli / Q000201:enzymology* / Q000378:metabolism*; D015394:Molecular Structure; D010204:Pantetheine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D000963:Antimetabolites; D010204:Pantetheine; D003577:Cytochrome P-450 Enzyme System; D000446:Aldehyde-Lyases; C054540:hydroperoxide lyase; D003065:Coenzyme A