Ascaroside activity in Caenorhabditis elegans is highly dependent on chemical structure.
The nematode Caenorhabditis elegans secretes ascarosides, structurally diverse derivatives of the 3,6-dideoxysugar ascarylose, and uses them in chemical communication. At high population densities, specific ascarosides, which are together known as the dauer pheromone, trigger entry into the stress-resistant dauer larval stage. In order to study the structure-activity relationships for the ascarosides, we synthesized a panel of ascarosides and tested them for dauer-inducing activity. This panel includes a number of natural ascarosides that were detected in crude pheromone extract, but as yet have no assigned function, as well as many unnatural ascaroside derivatives. Most of these ascarosides, some of which have significant structural similarity to the natural dauer pheromone components, have very little dauer-inducing activity. Our results provide a primer to ascaroside structure-activity relationships and suggest that slight modifications to ascaroside structure dramatically influence binding to the relevant G protein-coupled receptors that control dauer formation.
Department of Chemistry, Louisiana State University, Baton Rouge, 70803, United States.
Kyle A
KA
Hollister
Elizabeth S
ES
Conner
Xinxing
X
Zhang
Mark
M
Spell
Gary M
GM
Bernard
Pratik
P
Patel
Ana Carolina G V
AC
de Carvalho
Rebecca A
RA
Butcher
Justin R
JR
Ragains
D000818:Animals; D017173:Caenorhabditis elegans / Q000254:growth & development / Q000378:metabolism*; D006017:Glycolipids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D007814:Larva / Q000187:drug effects / Q000502:physiology; D010675:Pheromones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D006017:Glycolipids; D010675:Pheromones
Ascarosides; Caenorhabditis elegans; Dauer formation; Nematodes