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The origin of enantiodiscrimination is understood by performing the geometry optimization and energy minimization of the models of ternary complexes of (S)-mandelonitrile/(R)-mandelate/DAMP[H.sup.+] and (S)-mandelonitrile

Opioid peptides are key regulators in cellular and intercellular physiological responses, and could be therapeutically useful for modulating several pathological conditions. Unfortunately, the use of peptide-based agonists to target centrally located opioid receptors is limited by poor physicochemical (PC), distribution, metabolic, and pharmacokinetic (DMPK) properties that restrict penetration across the blood-brain barrier via passive diffusion. To address these problems, the present paper exploits fluorinated peptidomimetics to simultaneously modify PC and DMPK properties, thus facilitating entry into the central nervous system. As an initial example, the present paper exploited the Tyr 1 -ψ[( Z)CF═CH]-Gly 2 peptidomimetic to improve PC druglike characteristics (computational), plasma and microsomal degradation, and systemic and CNS distribution of Leu-enkephalin (Tyr-Gly-Gly-Phe-Leu). Thus, the fluoroalkene replacement transformed an instable in vitro tool compound into a stable and centrally distributed in vivo probe. In contrast, the Tyr 1 -ψ[CF 3 CH 2 -NH]-Gly 2 peptidomimetic decreased stability by accelerating proteolysis at the Gly 3 -Phe 4 position.

We describe the design, synthesis, and opioid activity of fluoroalkene (Tyr 1 -ψ[(Z)CF=CH]-Gly 2 ) and trifluoroethylamine (Tyr 1 -ψ[(S)/(R)-CF 3 CH-NH]-Gly 2 ) analogues of the endogenous opioid neuropeptide, Leu-enkephalin. The fluoroalkene peptidomimetic exhibited low nanomolar functional activity (5.0±2 nm and 60±15 nm for δ- and μ-opioid receptors, respectively) with a μ/δ-selectivity ratio that mimics that of the natural peptide. However, the trifluoroethylamine peptidomimetics, irrespective of stereochemistry, did not activate the opioid receptors, which suggest that bulky CF 3 substituents are not tolerated at this position., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Regioselective S-acylation of coenzyme A (CoA) is achieved under aqueous conditions using various aliphatic and aromatic carboxylic acids activated as their methyl acyl phosphate monoesters. Unlike many hydrophobic activating groups, the anionic methyl acyl phosphate mixed anhydride is more compatible with aqueous solvents, making it useful for conducting acylation reactions in an aqueous medium.