Arachidonoyl amino acids and arachidonoyl peptides: Synthesis and properties

Abstract

N-Arachidonoyl (AA) derivatives of amino acids (glycine, phenylalanine, proline, valine, gamma-amino butyric acid (GABA), dihydroxyphenylalanine, tyrosine, tryptophan, and alanine) and peptides (Semax, MEHFPGP, and PGP) were synthesized in order to study the biological properties of acylamino acids. The mass spectra of all the compounds at atmospheric pressure electrospray ionization display the most intense peaks of protonated molecular ions; the detection limits for these compounds are 10 fmol per sample. AA-Gly showed the highest inhibitory activity toward fatty acid amide hydrolase from rat brain (IC50 6.5 microM) among all the acylamino acids studied. AA-Phe, AA-Tyr, and AA-GABA exhibited a weak but detectable inhibitory effect (IC50 55, 60, and 50 microM, respectively). The acylated amino acids themselves, except for AA-Gly, were stable to the hydrolysis by this enzyme. All the arachidonoylamino acids inhibited cabbage phospholipase D to various degrees; AA-GABA and AA-Phe proved to be the most active (IC50 20 and 27 microM, respectively). Attempts to detect the biosynthesis of AA-Tyr in homogenates of rat liver and nerve tissue showed no formation in vitro of either this acylamino acid or AA-dopamine and AA-Phe, the products of its metabolism. The highest contents of these metabolites were detected in liver homogenate and in the brain homogenate, respectively. Acylamino acids exert no cytotoxic effect toward the glioma C6 cells. It was shown that N-acylation of Semax with arachidonic acid results in enhancement of its hydrolytic stability and increases its affinity for the sites of specific binding in rat cerebellum membranes. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2006, vol. 32, no. 3; see also http://www.maik.ru.

Environmental toxin acrolein alters levels of endogenous lipids, including TRP agonists: A potential mechanism for headache driven by TRPA1 activation

“…Currently, A-Phe lacks a known receptor target. One study reports that A-Phe is a mild inhibitor of FAAH (Bezuglov et al, 2006). The FAAH inhibiting activity of A-Phe may contribute to some of the altered lipoamine concentrations seen in acrolein treated rats.…”

A New Mechanism for Photo‐ and Radiation‐Induced Decomposition of Sphingolipids

“…Formation of the latter is possible due to C-C destruction of the species I: The established fact of photo-decomposition of CerPCho, due to the biological importance of this substance, is of particular interest. After photon absorption, CerPCho will undergo the Norrish type I decomposition: (8) hv R1 = -CH 2 O-P-OCH 2 CH 2 N(CH 3 …”

“…SPPtdCho was prepared by deacylation of CerPCho [7]. Synthesis of HPHA was performed according to a procedure based on acylation of amino alcohol with complex capric/n-butylcarbonic acid anhydride in a solvent system containing tetrahydrofuran and acetonitrile (1:2), with the addition of 15 lL of triethylamine per 10 mL of the mixture [8]. Structures of the synthesized compounds were confirmed by 1 H-and 13 C-NMR spectroscopy.…”

“…The alkyl radicals formed according to reaction (8) are capable of abstracting an H atom from the starting molecule and initiating the deamidation process, as described in [13]. Analysis of the reaction mixture obtained after photoinduced destruction of CerPCho (see Table 2) revealed the presence of 2-hexadecenal, stearamide and hydrocarbons, which may serve as confirmation for the reactions (8-10) taking place.…”

A Novel Pathway of Photoinduced Decomposition of Sphingolipids

“…Synthesis of N-(1,3-dihydroxypropan-2-yl)decanamide was performed according to a procedure based on acylation of serinol with a complex anhydride prepared from n-butylchloroformate and capric acid (10). To a solution of capric acid (0.17 g, 1 mmol) in 10 mL THF ⁄ acetonitrile (vol ⁄ vol, 1:2) was added 0.15 mL of triethylamine and cooled to )18°C.…”