Structure elucidation of two tryptophan-derived, high affinity Ah receptor ligands.
BACKGROUND
Environmental contaminants, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and other structurally related 'environmental hormones', exert their harmful biological effects through the Ah receptor signaling pathway. Several naturally occurring substances also bind to this receptor, but its natural role is still obscure. Tryptophan derivatives of the indolo[3,2-b]carbazole type, earlier suggested by us to be endogenous ligands for the receptor, should be a powerful tool in understanding receptor function. We therefore set out to determine their identity.


RESULTS
The two tryptophan-derived Ah receptor ligands have been chemically analyzed and characterized by means of mass spectrometry, 1H NMR and 13C NMR. UV, infra-red and fluorescence spectra were also recorded. All data are in accordance with the two compounds being closely related indolo[3,2-b]carbazole derivatives. Evidence is presented that compound A (MW = 312) is the symmetrical 6,12-diformylindolo[3,2-b]carbazole, and compound B (MW = 284) is the monosubstituted 6-formylindolo[3,2-b]carbazole.


CONCLUSIONS
The elucidation of the structures of the two high affinity Ah receptor ligands 6,12-diformylindolo[3,2-b]carbazole and 6-formylindolo[3,2-b]carbazole provides the necessary basis for further mechanistic studies of this important group of compounds, and will help in determining the natural role of the Ah receptor.
Rannug
U
U
Department of Genetic and Cellular Toxicology, Wallenberg Laboratory, Stockholm University, Sweden.
Rannug
A
A
Sjöberg
U
U
Li
H
H
Westerholm
R
R
Bergman
J
J
D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D010777:Photochemistry; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics / Q000378:metabolism* / Q000528:radiation effects; D013050:Spectrometry, Fluorescence; D013055:Spectrophotometry, Infrared; D013056:Spectrophotometry, Ultraviolet; D014364:Tryptophan / Q000737:chemistry / Q000378:metabolism* / Q000528:radiation effects; D014466:Ultraviolet Rays
D008024:Ligands; D018336:Receptors, Aryl Hydrocarbon; D014364:Tryptophan