Nitrated fatty acids (NO -FAs) act as anti-inflammatory signal mediators, albeit the molecular mechanisms behind NO -FAs' influence on diverse metabolic and signaling pathways in inflamed tissues are essentially elusive. Here, we combine fluorescence measurements with surface-specific sum frequency generation vibrational spectroscopy and coarse-grained computer simulations to demonstrate that NO -FAs alter lipid organization by accumulation at the membrane-water interface. As the function of membrane proteins strongly depends on both, protein structure as well as membrane properties, we consecutively follow the structural dynamics of an integral membrane protein in presence of NO -FAs.
View Article and Find Full Text PDFRay et al. (Reports, 29 July 2011, p. 637) assume that clozapine-N4-oxide (CNO) represents a "biologically inert synthetic ligand" that selectively activates the M4 muscarinic receptor-based DREADD (designer receptor exclusively activated by a designer drug).
View Article and Find Full Text PDFCertain amphibians provide themselves with a chemical defense by accumulating lipophilic alkaloids into skin glands from dietary arthropods. Examples of such alkaloids are pumiliotoxins (PTXs). In general, PTXs are known as positive modulators of voltage-gated sodium channels (VGSCs).
View Article and Find Full Text PDFThe aza-Claisen rearrangement of vinylpyrrolidines 1 yielded almost exclusively the trans-3,8-disubstituted nine-membered ring lactams 2 (TBS=tBuMe Si), independent of whether cis or trans isomers were used as starting materials. The conformation (which provided facial chirality) of the medium-sized ring controlled the regio- and diastereoselectivities of the transannular reactions that afforded indolizidinones 3.
View Article and Find Full Text PDFThe zwitterionic Claisen rearrangement of optically-active N-allyl pyrrolidines and various acid chlorides proceeds with high simple diastereoselection (internal asymmetric induction) and high 1,2-asymmetric induction, generating a new C-C bond adjacent to a chiral C-O function. The resulting gamma,delta-unsaturated amides were cyclized to the corresponding optically active gamma-butyrolactones, which are useful intermediates in natural product synthesis. On one hand, a diastereoselective iodocyclization of several lactones led to tetrahydrofurans with a substitution pattern representing a key intermediate of an oxa-prostaglandin synthesis.
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