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A novel pathway for lipid biosynthesis: the direct acylation of glycerol.

The acylation of glycerol-3-phosphate by acyl-CoA is regarded as the first committed step for the synthesis of the lipoidal moiety in glycerolipids. The direct acylation of glycerol in mammalian tissues has not been demonstrated. In this study, lipid biosynthesis in myoblasts and hepatocytes was reassessed by conducting pulse-chase experiments with [1,3-(3)H]glycerol. The results demonstrated that a portion of labeled glycerol was directly acylated to form monoacylglycerol and, subsequently, diacylglycerol and triacylglycerol. The direct acylation of glycerol became more prominent when the gly…

Superactivation of thermolysin by acylation with amino acid N-hydroxysuccinimide esters.

Synthesis of a series of active N-hydroxysuccinimide esters of aliphatic and aromatic amino acids has yielded a new class of reagents for th … unctional response. The increased activity is completely restored to that of the native enzyme by deacylation with nucleophiles, such as hydroxylamine, and the rate of restoration of native activity is a function of the particular acyl group incorporated. Preliminary evidence regarding the chemical properties of the modified enzyme suggests that tyrosine, r …

First synthesis of acylated nitrocyclopropanes.

Although nitrocyclopropanedicarboxylic acid esters are widely used in organic syntheses, nitrocyclopropanes with an acyl group have not yet been synthesized. When adducts of β-nitrostyrene and 1,3-dicarbonyl compounds are treated with (diacetoxyiodo)benzene and tetrabutylammonium iodide, iodination occurs at the α-position of the nitro group, and the subsequent O-attack of the enol moiety leads to 2,3-dihydrofuran. Cyclopropane was successfully synthesized through C-attack as the acyl group became bulkier. The obtained nitrocyclopropane was transformed into furan upon treatment with tin(II) ch

Protein acyl thioesterases (Review).

Many proteins are S-acylated, affecting their localization and function. Dynamic S-acylation in response to various stimuli has been seen for several proteins in vivo. The regulation of S-acylation is beginning to be elucidated. Proteins can autoacylate or be S-acylated by protein acyl transferases (PATs). Deacylation, on the other hand, is an enzymatic process catalyzed by protein thioesterases (APT1 and PPT1) but only APT1 appears to be involved in the regulation of the reversible S-acylation of cytoplasmic proteins seen in vivo. PPT1, on the other hand, is involved in the lysosomal degradat…

N-acyl migration in ceramides.

Upon exposure of truncated ceramides, such as N-acetyl-sphingenine, and long-chain ceramides to moderate acidic conditions, three derivatives are formed. Two of them turned out to be O-acylated sphingenine, 1-O- and 3-O-acyl-sphingenine, and the other was identified as sphingenine. Truncated dihydroceramides (e.g., N-acetyl- and N-hexanoyl-sphinganine) also show this type of rearrangement, which is therefore not related to the presence of the allylic hydroxy group or to the length of the N-acyl chain. Of particular concern is the fact that the O-acylated compounds, which can be considered sphi

An N-acyl Donor for Serine/Threonine Ligation Involving a Direct N-to-N Acyl Shift.

Developing precise peptide modification protocols is crucial for peptide-based drug development. While chemical ligation addresses this, conventional methods often face difficulties such as side reactions due to the high electrophilicity of S- or O-acyl donors. Here we developed an N-(2-formylphenyl)-hydroxamate (HDX) ester as an N-acyl donor for chemical ligation involving a direct N-to-N acyl shift, eliminating the need for S- or O-acyl compounds. Mechanistic studies revealed kinetic selectivity between substrates and the reversibility of the acyl shift, suggesting the possibility achieving

Direct and Enantioselective Acylation of Diverse C(sp3)-H Bonds with Aldehydes.

Chiral ketones containing α-aryl, α-amino, or α-oxy stereocenters are unique structural motifs found in numerous important natural products and pharmaceuticals, but their enantioselective synthesis remains a challenge. We report a synthetic method for the enantioselective acylation of diverse C(sp3)-H bonds by combining peroxide photosensitization and nickel catalysis. This method utilizes abundant and readily available aldehydes as an acyl source and is capable of acylating a variety of C(sp3)-H bonds, including benzylic, α-amino, and α-alkoxy C(sp3)-H bonds, with excellent enantioselectivity…

Selective O-Acylation of Ketones with Carboxylic Acids for Enol Esters Synthesis.

Selective O-acylation of ketones with carboxylic acids was disclosed, which produced a wide range of enol esters in good to high yields with Z-configured regioselectivity. This reaction showed high functional group tolerance and could be performed on a gram scale without any decrease of synthetic efficiency. When o-bromobenzoic acids were used, the corresponding enol esters could be easily derivatized into the value-added chromones via Claisen condensation tandem cyclization.

NaI-mediated α-keto-acylation of NH-sulfoximines with aryl methyl ketones.

A room-temperature NaI-mediated oxidative sulfoximidation of aryl methyl ketones to synthesize α-keto-N-acyl sulfoximines has been disclosed. This metal- and base-free NH-sulfoximidation is facilitated by tert-butyl hydroperoxide (TBHP) as the oxidant, affording α-ketoamides with good functional group tolerance, broad substrate scope, and scalability. Mechanistic investigations indicate the intermediacy of radicals and highlight molecular oxygen's significance as the oxygen source.

Photoelectrochemical Iron-Nickel Synergistic Catalysis for C(sp3)-H and Dehydroxymethylative Acylation.

We developed an iron-nickel dual-catalytic system for efficient C(sp3)-H activation acylation of hydrocarbons and carboxylic acids under photoelectrochemical conditions. This system is based on ligand-to-metal charge transfer-mediated direct hydrogen atom transfer and is applicable to inert C(sp3)-H-containing compounds. It also enables dehydroxymethylative acylation of alcohols, both these two reactions demonstrating broad substrate scope and unconventional chemoselectivity. Gram-scale synthesis, flow chemistry, and mechanistic studies highlight its potential in sustainable C(acyl)-C bond for…

Beyond Friedel-Crafts: Spontaneous and Fluoride-Catalyzed Acylation of 2-(Trialkylsilyl)pyridines.

2-(Trialkylsilyl)pyridines react spontaneously with acyl chlorides to give 2-pyridyl ketones in high yields. The process consists of four elementary steps of N-acylation, desilylation, C-acylation, and N-deacylation and results in a selective monosubstitution at the carbonyl group. The key step in this mechanism is the intrinsic generation of a stabilized ylide (Hammick intermediate), which acts as a nucleophile. For the functionalization of complex molecules, an alternative fluoride-catalyzed protocol utilizing more stable acyl fluorides has been developed.

Enantioselective Organocatalytic Desymmetric Acylation as an Access to Orthogonally Protected myo-Inositols.

Chiral cyclitols represent an important class of naturally occurring compounds. In particular, myo-inositol and its derivatives are essential for phosphorus storage and cell-signaling pathways in living organisms. Not surprisingly, these compounds constitute an emerging class of molecules with significant potential in both medicinal and synthetic chemistry. However, efficient catalytic methodologies for accessing chiral myo-inositol derivatives remain scarce. Herein, we report a metal-free, organocatalytic protocol for the desymmetric acylation of a readily available meso-myo-inositol diol. Th…

Hyper Cross-linked Poly(ether imide) via Friedel-Crafts Acylation and Dehydrochlorination.

Poly-(ether imide) (PEI), a high-performance thermoplastic, is known for its high mechanical strength, thermal stability, and great processa … ross-linked PEI through postpolymerization modification of the polymer backbone. Via Friedel-Crafts acylation with a thermally active moiety of 3-chloropropionyl chloride (3-CPC), the resulting P-(EI-CPC x ) retains solution processability and is used as an additive in virgin PEI, generating thermally stable and solvent-resistant PEI upon thermal annealing- …

Sequestering sequestosome 1 via S-acylation in autophagy, Huntington disease, and beyond.

Protein mislocalization and aggregation are hallmark features in neurodegeneration. As proteins mislocalize, proteostasis deficiency and protein aggregation typically follow. Autophagy is a crucial pathway for the removal of protein aggregates to maintain neuronal health, but is impaired in various neurodegenerative diseases, including Huntington disease (HD). We identified S-acylation, a reversible lipid modification of proteins, as an important regulator in protein trafficking and autophagy. SQSTM1 (sequestosome 1/p62) is an essential selective autophagy receptor for the sequestration of ubi…

S-ациляция и нейроинфламмация: терапевтический потенциал zDHC и модуляции децилазы.

Нейроинфламмация является отличительной чертой многих нейродегенеративных заболеваний, включая болезнь Альцгеймера, болезнь Паркинсона и Хантингтона, множественный склероз и инфантильный нейроидальный липофусциноз. Важным регулятором этих процессов является динамическое белковое С-асилирование, обратимое липидное послепереходное изменение. С-ациляция стимулируется zDHC palmitoil aciltransfases, а удаление ацильных групп - ацилпротеиновыми тиоэстеразами. С-асилация контролирует локализацию, стабильность и функцию около 48% всех белков в нервной системе, включая синаптические скафольды, ионные к

Совпадение в аннотации оригинала
Neuroinflammation is a hallmark of many neurodegenerative diseases, including Alzheimer's, Parkinson's and Huntington's disease, multiple sclerosis, and infantile neuronal ceroid lipofuscinosis. Dynamic protein S-acylation, a reversible lipid post-translational modification, is an important regulator in these processes. S-acylation is catalysed by the zDHHC …

Plasma Membrane Association by N-Acylation Governs PKG Function in Toxoplasma gondii.

Cyclic GMP (cGMP)-dependent protein kinase (protein kinase G [PKG]) is essential for microneme secretion, motility, invasion, and egress in apicomplexan parasites, However, the separate roles of two isoforms of the kinase that are expressed by some apicomplexans remain uncertain. Despite having identical regulatory and catalytic domains, PKGI is plasma membrane associated whereas PKGII is cytosolic in Toxoplasma gondii To determine whether these isoforms are functionally distinct or redundant, we developed an auxin-inducible degron (AID) tagging system for conditional protein depletion in T. g

Effect of N-Terminal Acylation on the Activity of Myostatin Inhibitory Peptides.

Inhibition of myostatin, which negatively regulates skeletal muscle growth, is a promising strategy for the treatment of muscle atrophic disorders, such as muscular dystrophy, cachexia and sarcopenia. Recently, we identified peptide A (H-WRQNTRYSRIEAIKIQILSKLRL-NH2 ), the 23-amino-acid minimum myostatin inhibitory peptide derived from mouse myostatin prodomain, and highlighted the importance of its N-terminal tryptophan residue for the effective inhibition. In this study, we synthesized a series of acylated peptide derivatives focused on the tryptophan residue to develop potent myostatin inhib

Reactions of alpha-boranophosphorus compounds with electrophiles: alkylation, acylation, and other reactions.

The homologation of phosphorus carbenoids with organoboranes leads to alpha-boranophosphorus compounds, which can be further functionalized through reactions with various electrophiles, either directly or after activation to the corresponding borate. A variety of substituted organophosphorus compounds can be obtained in one pot via reaction with many electrophiles. Complex structures are prepared in a single step using simple building blocks.

In vitro fatty acid acylation of mucus glycoprotein from sublingual salivary glands.

The enzyme activity which catalyzes the transfer of palmitic acid from palmitoyl-coenzyme A to sublingual gland mucus glycoprotein has been demonstrated in the detergent extracts of the microsomal fraction of rat sublingual and parotid salivary glands. The acyltransferase activity of this fraction was similar in both types of glands. Further subcellular fractionation performed on sublingual glands revealed that the enzyme is associated with the Golgi-rich membrane fraction. Optimum enzymatic activity for fatty acylation of mucus glycoprotein was obtained using 0.5% Triton X-100, 2 mM dithiothr…