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International Journal of Biological... Mar 2022The covalent grafting of alkyl gallates onto pectin using a lipase-catalyzed reaction in a tetrahydrofuran/aqueous medium process acylated pectin molecules with...
The covalent grafting of alkyl gallates onto pectin using a lipase-catalyzed reaction in a tetrahydrofuran/aqueous medium process acylated pectin molecules with excellent antioxidant and antibacterial properties. The alkyl gallates including methyl, ethyl, and propyl gallates were enzymatically grafted onto pectin molecule, in order to study the effect of alkyl gallates on the functional modification of pectin. The grafting mechanism was analyzed by ultraviolet-visible spectrum (UV-Vis), Fourier transform infrared spectrum (FTIR), proton nuclear magnetic resonance (HNMR), and density functional theory (DFT). Results suggested that lipase grafted 4-OH of alkyl gallate onto pectin by catalyzing esterification in organic/aqueous solution, and the grafting rate was affected by the length of alkyl chain of the gallates molecule. In vitro experiments, the acylated pectins exhibited stronger antioxidant activity in the DPPH test and β-carotene bleaching test and were found to have obvious antimicrobial performance against Escherichia coli and Staphylococcus aureus.
Topics: Acylation; Density Functional Theory; Gallic Acid; Pectins; Staphylococcus aureus
PubMed: 35038471
DOI: 10.1016/j.ijbiomac.2022.01.070 -
SLAS Discovery : Advancing Life... Feb 2020Protein acylation, exemplified by lysine acetylation, is a type of indispensable and widespread protein posttranslational modification in eukaryotes. Functional...
Protein acylation, exemplified by lysine acetylation, is a type of indispensable and widespread protein posttranslational modification in eukaryotes. Functional annotation of various lysine acetyltransferases (KATs) is critical to understanding their regulatory roles in abundant biological processes. Traditional radiometric and immunosorbent assays have found broad use in KAT study but have intrinsic limitations. Designing acyl-coenzyme A (CoA) reporter molecules bearing chemoselective chemical warhead groups as surrogates of the native cofactor acetyl-CoA for bioorthogonal labeling of KAT substrates has come into a technical innovation in recent years. This chemical biology platform equips molecular biologists with empowering tools in acyltransferase activity detection and substrate profiling. In the bioorthogonal labeling, protein substrates are first enzymatically modified with a functionalized acyl group. Subsequently, the chemical warhead on the acyl chain conjugates with either an imaging chromophore or an affinity handle or any other appropriate probes through an orthogonal chemical ligation. This bioorganic strategy reformats the chemically inert acetylation and acylation marks into a chemically maneuverable functionality and generates measurable signals without recourse to radioisotopes or antibodies. It offers ample opportunities for facile sensitive detection of KAT activity with temporal and spatial resolutions as well as allows for chemoproteomic profiling of protein acetylation pertaining to specific KATs of interest on the global scale. We reviewed here the past and current advances in bioorthogonal protein acylations and highlighted their wide-spectrum applications. We also discussed the design of other related acyl-CoA and CoA-based chemical probes and their deployment in illuminating protein acetylation and acylation biology.
Topics: Acetylation; Acyl Coenzyme A; Acylation; Humans; Lysine; Lysine Acetyltransferases; Protein Processing, Post-Translational; Proteins
PubMed: 31711353
DOI: 10.1177/2472555219887144 -
Talanta Jan 2023for the analysis of cannabinoids in bio-matrices are continually improved to achieve best possible sensitivity in their detection and accurate quantification. It has...
for the analysis of cannabinoids in bio-matrices are continually improved to achieve best possible sensitivity in their detection and accurate quantification. It has been well documented that CBD cyclizes to Δ9-THC and Δ9-THC isomerizes to Δ8-THC under acidic conditions by means of a Lewis-acid-catalyzed process, causing difficulty in accurate quantification of Δ9-THC in the presence of CBD, of CBD itself and of Δ9-THC itself when these compounds have to be derivatized by acylation. The present paper shows that CBD cyclization and Δ9-THC isomerization can be blocked by tertiary amines or azines, which capture protons appearing in the derivatizing mixture during acylation. The efficiency of the described acylation of CBD depends on the time and temperature of the derivatizing process, whereas the degree of CBD acylation, i.e. the synthesis of mono- or di-acylate CBD derivative, depends on the mutual ratio of the cannabinoid, the acylating agent and the proton binding compound. The way of mono- and di-acyl CBD derivatives formation described in the paper has not been reported yet. The paper contains a comprehensive analytical characterization of two types of CBD acyl derivatives, CBD-TFA and CBD-Ac, obtained by NMR, GC-MS and LC-MS.
Topics: Acylation; Amines; Cannabidiol; Cannabinoids; Dronabinol; Protons
PubMed: 36075144
DOI: 10.1016/j.talanta.2022.123777 -
Protein Science : a Publication of the... Dec 2017The Hippo pathway is deregulated in various cancers, and the discovery of molecules that modulate this pathway may open new therapeutic avenues in oncology. TEA/ATTS...
The Hippo pathway is deregulated in various cancers, and the discovery of molecules that modulate this pathway may open new therapeutic avenues in oncology. TEA/ATTS domain (TEAD) transcription factors are the most distal elements of the Hippo pathway and their transcriptional activity is regulated by the Yes-associated protein (YAP). Amongst the various possibilities for targeting this pathway, inhibition of the YAP:TEAD interaction is an attractive strategy. It has been shown recently that TEAD proteins are covalently linked via a conserved cysteine to a fatty acid molecule (palmitate) that binds to a deep hydrophobic cavity present in these proteins. This acylation of TEAD seems to be required for efficient binding to YAP, and understanding how it modulates the YAP:TEAD interaction may provide useful information on the regulation of TEAD function. In this report we have studied the effect of TEAD4 acylation on its interaction with YAP and the other co-activator transcriptional co-activator with PDZ-binding motif (TAZ). We show in our biochemical and cellular assays that YAP and TAZ bind in a similar manner to acylated and non-acylated TEAD4. This indicates that TEAD4 acylation is not a prerequisite for its interaction with YAP or TAZ. However, we observed that TEAD4 acylation significantly enhances its stability, suggesting that it may help this transcription factor to acquire and/or maintain its active conformation.
Topics: Acylation; Adaptor Proteins, Signal Transducing; DNA-Binding Proteins; Humans; Intracellular Signaling Peptides and Proteins; Models, Molecular; Muscle Proteins; Phosphoproteins; Signal Transduction; TEA Domain Transcription Factors; Trans-Activators; Transcription Factors; Transcriptional Coactivator with PDZ-Binding Motif Proteins; YAP-Signaling Proteins
PubMed: 28960584
DOI: 10.1002/pro.3312 -
The Journal of Organic Chemistry Nov 2022Starting from -bromostyrenes, 12 6,7-benzotropolones were synthesized in 3 or 4 steps. Br/Li exchanges provided the respective -lithiostyrenes. The latter were acylated...
Starting from -bromostyrenes, 12 6,7-benzotropolones were synthesized in 3 or 4 steps. Br/Li exchanges provided the respective -lithiostyrenes. The latter were acylated by a Weinreb amide, if unhindered, or hydroxyalkylated by an aldehyde, if hindered (an oxidation ensuing thereafter). Acetonide-containing benzannulated nonatrienones resulted. Ring-closing olefin metatheses converted them into acetonide-containing benzocycloheptadienones. Treatment with aq. HCl caused hydrolyses followed by β-elimination reactions giving 6,7-benzotropolones.
Topics: Hydrolysis; Biflavonoids; Alkenes; Acylation
PubMed: 36318761
DOI: 10.1021/acs.joc.2c01968 -
Angewandte Chemie (International Ed. in... Sep 2022Thioesterases (TEs) are fundamentally important enzymes present in all bacteria and eukaryotes, where they have conserved functions in fatty acid biosynthesis and...
Thioesterases (TEs) are fundamentally important enzymes present in all bacteria and eukaryotes, where they have conserved functions in fatty acid biosynthesis and secondary metabolism. This work provides the first structural insights into a functionally distinct group of TEs that perform diverse acylations in polyketide and peptide biosynthesis (TE s). Structural analysis of the oocydin (OocS) TE domain facilitated identification and engineering of the active site to modulate acyl-group acceptance. In this way, we achieved higher reactivity using a structure-based approach, building a foundation for biocatalytic development of TE -mediated O-acylation, a modification known to improve the bioactivity of oocydin-type polyketides. Lastly, the promiscuity of the OocS TE motivated us to investigate, and ultimately provide evidence for, the production of longer chain branched oocydins in the native host Serratia plymuthica 4Rx13. This work frames the OocS TE and homologs as invaluable synthetic biology tools for polyketide drug development.
Topics: Acylation; Catalytic Domain; Fatty Acids; Polyketide Synthases; Polyketides; Secondary Metabolism
PubMed: 35903999
DOI: 10.1002/anie.202206385 -
Angewandte Chemie (International Ed. in... Jul 2019The site-selective functionalization of carbohydrates is an active area of research. Reported here is the surprising observation that the sterically encumbered adamantyl...
The site-selective functionalization of carbohydrates is an active area of research. Reported here is the surprising observation that the sterically encumbered adamantyl group directed site-selective acylation at the C2 position of S-glycosides through dispersion interactions between the adamantyl C-H bonds and the π system of the cationic acylated catalyst, which may have broad implications in many other chemical reactions. Because of their stability, chemical orthogonality, and ease of activation for glycosylation, the site-selective acylation of S-glycosides streamlines oligosaccharide synthesis and will have wide applications in complex carbohydrate synthesis.
Topics: Acylation; Catalysis; Glycosylation; Humans; Oligosaccharides
PubMed: 31066162
DOI: 10.1002/anie.201903587 -
Food Chemistry May 2022In this work, ring-like anhydrides (C4, C5, and C6) with different sizes and succinic anhydrides (C4, C10, C12, C14, and C16) with different side chain lengths were used...
In this work, ring-like anhydrides (C4, C5, and C6) with different sizes and succinic anhydrides (C4, C10, C12, C14, and C16) with different side chain lengths were used to modify bovine bone gelatin (BBG) and cold-water fish skin gelatin (CFG), and the effect of acylated gelatins on fish oil-loaded emulsions stability was explored. The results showed that the degree of N-acylation decreased with increased ring sizes or side chain lengths, and the surface hydrophobicity of acylated gelatins increased with increased anhydride carbon numbers. Acylated CFGs had higher droplet stability and lower liquid-gel transition time than acylated BBGs. Only BBG-C12 had a slight increase on the creaming stability among these acylated gelatins. These results demonstrated that the gelatins could be modified by all the anhydrides and their emulsion stabilization ability was dependent on the gelatin type and anhydride structure. The results could be beneficial for protein-based emulsifier development and application.
Topics: Acylation; Anhydrides; Animals; Cattle; Emulsions; Gelatin; Succinic Anhydrides
PubMed: 34954583
DOI: 10.1016/j.foodchem.2021.131882 -
Food Chemistry Feb 2022In this paper, the effects of acylation modification on the gel behavior of ovalbumin (OVA) under heating induction have been investigated. From the obtained results,...
In this paper, the effects of acylation modification on the gel behavior of ovalbumin (OVA) under heating induction have been investigated. From the obtained results, the acylated OVA hydrogels exhibited superior gelation properties than the native OVA hydrogels (NOVA-G) in terms of light transmission, gel hardness, resilience and water holding capacity. SEM revealed acylation modifications effectively promoted the formation of uniform and dense network structure of OVA hydrogels. The main intermolecular forces of the acylation-modified OVA hydrogels were hydrophobic interactions and hydrogen bonding. FTIR showed that acylation modifications caused 26.2% decrease in α-helix and 59.2% increase in β-sheet content compared to NOVA-G. Furthermore, in-vitro release experiments showed that the release rate of curcumin from acylated OVA hydrogels was significantly delayed. Moreover, the above results have shown that acylation modifications can be considered as an effective method to improve the gelation as well as drug release properties of protein hydrogels.
Topics: Acylation; Hot Temperature; Hydrogels; Hydrophobic and Hydrophilic Interactions; Ovalbumin
PubMed: 34479008
DOI: 10.1016/j.foodchem.2021.130912 -
Pharmaceutical Research Aug 2014To prepare acylated exenatide analogues and investigate their biological properties for guiding the development of PLGA formulations of exenatide.
PURPOSE
To prepare acylated exenatide analogues and investigate their biological properties for guiding the development of PLGA formulations of exenatide.
METHODS
The acylated exenatide analogues were prepared by reaction with glycolic acid (GA), one constitutional unit of PLGA, and characterized by HPLC-MS/MS and Circular Dichroism (CD). The pharmacokinetic properties and anti-diabetic activities were studied in SD rats and db/db mice, respectively.
RESULTS
Structural characterizations of the acylated products showed that one to four glycolic acids (GAs) were connected to the primary amine groups of exenatide, and there was a conversion of α-helix to β-sheet to some extent. Pharmacokinetic studies in SD rats revealed that acylated exenatides had a similar Tmax with that of the prototype drug, whereas the Cmax and the AUC values of the adducts were significantly decreased. Biological activity tests demonstrated that exenatide and acylated exenatide analogues had similar in vivo antidiabetic activities in terms of controlling blood glucose concentration, HbA1c level, body weight and food intake.
CONCLUSIONS
These findings suggest that GA conjugated exenatide had no influence on the peptide efficacy, therefore it's not necessary to inhibit exenatide acylation in PLGA formulations during the peptide release process.
Topics: Acylation; Animals; Diabetes Mellitus, Type 2; Exenatide; Glycolates; Hypoglycemic Agents; Male; Mice; Mice, Transgenic; Peptides; Rats; Rats, Sprague-Dawley; Venoms
PubMed: 24549820
DOI: 10.1007/s11095-014-1298-2