42249-40-1

Usage

InChI:InChI=1/C16H28N3O/c1-15(2)10-13(11-16(3,4)19(15)20)18-14(17)12-8-6-5-7-9-12/h10,12H,5-9,11H2,1-4H3,(H2,17,18)

Upstream product

• 826-36-8 2,2,6,6-Tetramethyl-4-piperidone 
• 45985-26-0 4-oxo-2,2,6,6-tetramethylpiperidin-oxyl 
• 14691-88-4 4-amino-2,2,6,6-tetramethyl-1-piperidine-1-oxyl 

Relevant academic research and scientific papers

EPR Studies of V-ATPase with Spin-Labeled Inhibitors DCC and Archazolid: Interaction Dynamics with Proton Translocating Subunit c

Vacuolar-type H+-ATPases (V-ATPases) have gained recent attention as highly promising anticancer drug targets, and therefore detailed structural analyses and studies of inhibitor interactions are very important research objectives. Spin labeling of the V-ATPase holoenzyme from the tobacco hornworm Manduca sexta and V-ATPase in isolated yeast (Saccharomyces cerevisiae) vacuoles was accomplished by two novel methods involving the covalent binding of a (2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO) derivative of N,N′-dicyclohexylcarbodiimide (DCC) to the essential glutamate residue in the active site and the noncovalent interaction of a radical analogue of the highly potent inhibitor archazolid, a natural product from myxobacteria. Both complexes were evaluated in detail by electron paramagnetic resonance (EPR) spectroscopic studies and double electron-electron resonance (DEER) measurements, revealing insight into the inhibitor binding mode, dynamics, and stoichiometry as well as into the structure of the central functional subunit c of these medicinally important hetero-multimeric proton-translocating proteins. This study also demonstrates the usefulness of natural product derived spin labels as tools in medicinal chemistry. Near and DEER: Electron paramagnetic resonance (EPR) and double electron-electron resonance (DEER) studies of V-ATPase in complex with spin-labeled inhibitors DCC and archazolid have enabled insight into the noncovalent binding dynamics and analysis of the enzyme′s key functional subunit c. These studies also demonstrate the general utility of natural product derived spin labels as innovative tools for chemical biology.

Design, Synthesis, EPR-Studies and Conformational Bias of Novel Spin-Labeled DCC-Analogues for the Highly Regioselective Labeling of Aliphatic and Aromatic Carboxylic Acids

Novel types of spin-labeled N,N′-dicyclohexylcarbodiimides (DCC) are reported that bear a 2,2,6,6-tetramethylpiperidinyloxyl (TEMPO) residue on one side and different aromatic and aliphatic cyclohexyl analogues on the other side of the diimide core. These readily available novel reagents add efficiently to aliphatic and aromatic carboxylic acids, forming two possible spin-labeled amide derivatives with different radical distances of the resulting amide. The addition of aromatic DCC analogues proceeds with excellent selectivity, giving amides where the carboxylic acid is exclusively connected to the aromatic residue, while little or no selectivity was observed for the aliphatic congeners. The usefulness of these adducts in structural studies was demonstrated by EPR (electron paramagnetic resonance) measurements of biradical adducts of biphenyl-4,4′-dicarboxylic acids. These analyses also reveal high degrees of conformational bias for aromatic DCC derivatives, which further underlines the powerfulness of these novel reagents. This observation was further corroborated by quantum chemical calculations, giving a detailed understanding of the structural dynamics, while detailed information on the solid state structure of all novel reagents was obtained by X-ray structure analyses.