Upon controlled microwave heating and using cyanuric chloride as a coupling reagent, an efficient... more Upon controlled microwave heating and using cyanuric chloride as a coupling reagent, an efficient amidation procedure for the synthesis of 1,3-dihydro-2H-benzo[d]imidazol-2-one-based agonists of TRPC3/6 ion channels has been developed. Compared to the few conventional protocols, a drastic reduction in processing time from ca. 2 days down to 10 minutes was achieved accompanied by significantly improved product yields. The robustness of the method was confirmed by 18 additional examples including aromatic, aliphatic, and heterocyclic amines and acids. The obtained agonists were screened for biological activity at 1 μM concentration and few structure-activity relations have been established.
Photouncaging of second messengers has been successfully employed to gain mechanistic insight of ... more Photouncaging of second messengers has been successfully employed to gain mechanistic insight of cellular signaling pathways. One of the most enigmatic processes of ion channel regulation is lipid recognition and lipid-gating of TRPC channels, which represents pivotal mechanisms of cellular Ca(2+) homeostasis. Recently, optopharmacological tools including caged lipid mediators became available, enabling an unprecedented level of temporal and spatial control of the activating lipid species within a cellular environment. Here we tested a commonly used caged ligand approach for suitability to investigate TRPC signaling at the level of membrane conductance and cellular Ca(2+) handling. We report a specific photouncaging artifact that is triggered by the cage structure coumarin at UV illumination. Electrophysiological characterization identified a light-dependent membrane effect of coumarin. UV light (340 nm) as used for photouncaging, initiated a membrane conductance specifically in the presence of coumarin as low as 30 μmol L(-1) concentrations. This conductance masked the TRPC3 conductance evoked by photouncaging, while TRPC-mediated cellular Ca(2+) responses were largely preserved. The observed light-induced membrane effects of the released caging moiety may well interfere with certain cellular functions, and prompt caution in using coumarin-caged second messengers in cellular studies.
This article has been temporarily removed whilst further analysis is undertaken. It will be made ... more This article has been temporarily removed whilst further analysis is undertaken. It will be made available again soon.
... 8 S. W. Djuric, N. Y. BaMaung, A. Basha, ; H. Liu, J. R. Luly, D. J. Madar, R. J. Sciotti, N.... more ... 8 S. W. Djuric, N. Y. BaMaung, A. Basha, ; H. Liu, J. R. Luly, D. J. Madar, R. J. Sciotti, N. P. Tu, F. L. Wagenaar, P. E. Wiedeman, X. Zhou, S. Ballaron, J. Bauch, Y.-W. Chen, X. G ... 11c M. Irfan, E. Petricci, T. N. Glasnov, M. Taddei, C. O. Kappe, Eur. J. Org. Chem. 2009, 1327–1334. ...
European Journal of Organic Chemistry, Feb 2, 2009
... Irfan, M., Petricci, E., Glasnov, TN, Taddei, M. and Kappe, CO (2009), Continuous Flow Hydrog... more ... Irfan, M., Petricci, E., Glasnov, TN, Taddei, M. and Kappe, CO (2009), Continuous Flow Hydrogenation of Functionalized Pyridines. ... nicotinate, 7). The partial hydrogenation product is the vinylogous carbamate 8 (Scheme 3), which is stabilized by conjugation of the lone-pair of ...
Upon controlled microwave heating and using cyanuric chloride as a coupling reagent, an efficient... more Upon controlled microwave heating and using cyanuric chloride as a coupling reagent, an efficient amidation procedure for the synthesis of 1,3-dihydro-2H-benzo[d]imidazol-2-one-based agonists of TRPC3/6 ion channels has been developed. Compared to the few conventional protocols, a drastic reduction in processing time from ca. 2 days down to 10 minutes was achieved accompanied by significantly improved product yields. The robustness of the method was confirmed by 18 additional examples including aromatic, aliphatic, and heterocyclic amines and acids. The obtained agonists were screened for biological activity at 1 μM concentration and few structure-activity relations have been established.
Photouncaging of second messengers has been successfully employed to gain mechanistic insight of ... more Photouncaging of second messengers has been successfully employed to gain mechanistic insight of cellular signaling pathways. One of the most enigmatic processes of ion channel regulation is lipid recognition and lipid-gating of TRPC channels, which represents pivotal mechanisms of cellular Ca(2+) homeostasis. Recently, optopharmacological tools including caged lipid mediators became available, enabling an unprecedented level of temporal and spatial control of the activating lipid species within a cellular environment. Here we tested a commonly used caged ligand approach for suitability to investigate TRPC signaling at the level of membrane conductance and cellular Ca(2+) handling. We report a specific photouncaging artifact that is triggered by the cage structure coumarin at UV illumination. Electrophysiological characterization identified a light-dependent membrane effect of coumarin. UV light (340 nm) as used for photouncaging, initiated a membrane conductance specifically in the presence of coumarin as low as 30 μmol L(-1) concentrations. This conductance masked the TRPC3 conductance evoked by photouncaging, while TRPC-mediated cellular Ca(2+) responses were largely preserved. The observed light-induced membrane effects of the released caging moiety may well interfere with certain cellular functions, and prompt caution in using coumarin-caged second messengers in cellular studies.
This article has been temporarily removed whilst further analysis is undertaken. It will be made ... more This article has been temporarily removed whilst further analysis is undertaken. It will be made available again soon.
... 8 S. W. Djuric, N. Y. BaMaung, A. Basha, ; H. Liu, J. R. Luly, D. J. Madar, R. J. Sciotti, N.... more ... 8 S. W. Djuric, N. Y. BaMaung, A. Basha, ; H. Liu, J. R. Luly, D. J. Madar, R. J. Sciotti, N. P. Tu, F. L. Wagenaar, P. E. Wiedeman, X. Zhou, S. Ballaron, J. Bauch, Y.-W. Chen, X. G ... 11c M. Irfan, E. Petricci, T. N. Glasnov, M. Taddei, C. O. Kappe, Eur. J. Org. Chem. 2009, 1327–1334. ...
European Journal of Organic Chemistry, Feb 2, 2009
... Irfan, M., Petricci, E., Glasnov, TN, Taddei, M. and Kappe, CO (2009), Continuous Flow Hydrog... more ... Irfan, M., Petricci, E., Glasnov, TN, Taddei, M. and Kappe, CO (2009), Continuous Flow Hydrogenation of Functionalized Pyridines. ... nicotinate, 7). The partial hydrogenation product is the vinylogous carbamate 8 (Scheme 3), which is stabilized by conjugation of the lone-pair of ...
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