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.
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.
Authors: Julia Tigges; Thomas Haarmann-Stemmann; Christoph F A Vogel; Annemarie Grindel; Ulrike Hübenthal; Heidi Brenden; Susanne Grether-Beck; Gabriele Vielhaber; William Johncock; Jean Krutmann; Ellen Fritsche Journal: J Invest Dermatol Date: 2013-08-30 Impact factor: 8.551
Authors: Tiffany Hughes; Edward L Briercheck; Aharon G Freud; Rossana Trotta; Susan McClory; Steven D Scoville; Karen Keller; Youcai Deng; Jordan Cole; Nicholas Harrison; Charlene Mao; Jianying Zhang; Don M Benson; Jianhua Yu; Michael A Caligiuri Journal: Cell Rep Date: 2014-06-19 Impact factor: 9.423
Authors: Sagie Wagage; Beena John; Bryan L Krock; Aisling O'Hara Hall; Louise M Randall; Christopher L Karp; M Celeste Simon; Christopher A Hunter Journal: J Immunol Date: 2014-01-08 Impact factor: 5.422
Authors: K Gradin; J McGuire; R H Wenger; I Kvietikova; M L fhitelaw; R Toftgård; L Tora; M Gassmann; L Poellinger Journal: Mol Cell Biol Date: 1996-10 Impact factor: 4.272