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1210-83-9Relevant academic research and scientific papers
Knockout of arabidopsis serotonin N-acetyltransferase-2 reduces melatonin levels and delays flowering
Lee, Hyoung Yool,Lee, Kyungjin,Back, Kyoungwhan
, (2019)
Melatonin plays roles in both plant growth and defense. Serotonin N-acetyltransferase (SNAT) catalyzes formation of N-acetylserotonin (NAS) from serotonin. Plants contain two SNAT isogenes, which exhibit low-level amino acid homology. We studied the Arabidopsis thaliana SNAT2 (AtSNAT2) gene; we prepared recombinant SNAT2 protein and characterized a snat2 knockout mutant. The SNAT2 protein exhibited 27% amino acid homology with SNAT1; the Km was 232 μM and the Vmax was 2160 pmol/min/mg protein. Melatonin inhibited SNAT enzyme activity in vitro. SNAT2 mRNA was abundantly expressed in flowers; the melatonin content of flowers of the snat2 mutant was significantly less than that of wild-type flowers. The mutant exhibited delayed flowering and reductions in leaf area and biomass compared to the wild type. Delayed flowering was attributable to reductions in the expression levels of the gibberellin biosynthetic genes ent-kaurene synthase (KS) and FLOWERING LOCUS T (FT).
Synthesis and evaluation of the antiovulatory activity of a variety of melatonin analogues
Flaugh,Crowell,Clemens,Sawyer
, p. 63 - 69 (1979)
A series of melatonin analogues was synthesized and examined for ovulation-blocking activity. Deviation from the 5-methoxy group or substitution of the 1 position prevented activity. Activity was not particularly sensitive to minor variations in the N-acyl group nor was it significantly altered by methylation of position 2 or the α-methylene; however, a pronounced enhancement resulted from halogenation of the 6 position.
Mutasynthesis of Physostigmines in Myxococcus xanthus
Winand, Lea,Schneider, Pascal,Kruth, Sebastian,Greven, Nico-Joel,Hiller, Wolf,Kaiser, Marcel,Pietruszka, J?rg,Nett, Markus
, p. 6563 - 6567 (2021)
The alkaloid physostigmine is an approved anticholinergic drug and an important lead structure for the development of novel therapeutics. Using a complementary approach that merged chemical synthesis with pathway refactoring, we produced a series of physostigmine analogues with altered specificity and toxicity profiles in the heterologous host Myxococcus xanthus. The compounds that were generated by applying a simple feeding strategy include the promising drug candidate phenserine, which was previously accessible only by total synthesis.
Synthesis process of melatonin intermediate N-acetyl serotonin
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Paragraph 0026-0041, (2021/09/15)
The invention relates to the technical field of biological semi-synthesis, and provides a synthesis process of a melatonin intermediate N-acetyl serotonin, wherein the synthesis process comprises the following steps: S1, adding serotonin hydrochloride into dichloromethane, and stirring; S2, adding triethylamine and sodium bicarbonate, stirring into a suspension, and cooling in the process; S3, adding an acetylation reagent; S4, heating and stirring the reaction mixture; and S5, after the reaction is finished, carrying out post-treatment. According to the technical scheme, the problems that in the prior art, the technological process is complex, and the product quality is poor are solved.
BIOMARKER PANEL TARGETED TO DISEASES DUE TO MULTIFACTORIAL ONTOLOGY OF GLYCOCALYX DISRUPTION
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, (2021/04/02)
The present disclosure provides biomarkers useful as companion diagnostics for detecting glycocalyx-based disease that is amenable to treatment using compounds designed for improving the condition of the glycocalyx and/or reducing inflammation and/or oxidative damage, as well as related compositions, kits, and methods.
Biocatalytic C3-Indole Methylation—A Useful Tool for the Natural-Product-Inspired Stereoselective Synthesis of Pyrroloindoles
Schneider, Pascal,Hen?en, Birgit,Paschold, Beatrix,Chapple, Benjamin P.,Schatton, Marcel,Seebeck, Florian P.,Classen, Thomas,Pietruszka, J?rg
, p. 23412 - 23418 (2021/09/20)
Enantioselective synthesis of bioactive compounds bearing a pyrroloindole framework is often laborious. In contrast, there are several S-adenosyl methionine (SAM)-dependent methyl transferases known for stereo- and regioselective methylation at the C3 position of various indoles, directly leading to the formation of the desired pyrroloindole moiety. Herein, the SAM-dependent methyl transferase PsmD from Streptomyces griseofuscus, a key enzyme in the biosynthesis of physostigmine, is characterized in detail. The biochemical properties of PsmD and its substrate scope were demonstrated. Preparative scale enzymatic methylation including SAM regeneration was achieved for three selected substrates after a design-of-experiment optimization.
Characterization of arylalkylamine n-acyltransferase from tribolium castaneum: an investigation into a potential next-generation insecticide target
Anderson, Ryan L.,Chen, Yu,Gelis, Ioannis,Leahy, James W.,Lewandowski, Eric M.,Mccaskey, Angelica N.,Merkler, David J.,O'flynn, Brian G.,Prins, Karin Claire,Rios-Guzman, Nasha M.,Shepherd, Britney A.,Suarez, Gabriela
, p. 513 - 523 (2020/03/11)
The growing issue of insecticide resistance has meant the identification of novel insecticide targets has never been more important. Arylalkylamine N-acyltransferases (AANATs) have been suggested as a potential new target. These promiscuous enzymes are involved in the N-acylation of biogenic amines to form N-acylamides. In insects, this process is a key step in melanism, hardening of the cuticle, removal of biogenic amines, and in the biosynthesis of fatty acid amides. The unique nature of each AANAT isoform characterized indicates each organism accommodates an assembly of discrete AANATs relatively exclusive to that organism. This implies a high potential for selectivity in insecticide design, while also maintaining polypharmacology. Presented here is a thorough kinetic and structural analysis of AANAT found in one of the most common secondary pests of all plant commodities in the world, Tribolium castaneum. The enzyme, named TcAANAT0, catalyzes the formation of short-chain N-acylarylalkylamines, with short-chain acyl-CoAs (C2-C10), benzoyl-CoA, and succinyl-CoA functioning in the role of acyl donor. Recombinant TcAANAT0 was expressed and purified from E. coli and was used to investigate the kinetic and chemical mechanism of catalysis. The kinetic mechanism is an ordered sequential mechanism with the acyl-CoA binding first. pH-rate profiles and site-directed mutagenesis studies identified amino acids critical to catalysis, providing insights about the chemical mechanism of TcAANAT0. A crystal structure was obtained for TcAANAT0 bound to acetyl-CoA, revealing valuable information about its active site. This combination of kinetic analysis and crystallography alongside mutagenesis and sequence analysis shines light on some approaches possible for targeting TcAANAT0 and other AANATs for novel insecticide design.
Flow-based enzymatic synthesis of melatonin and other high value tryptamine derivatives: A five-minute intensified process
Contente, Martina Letizia,Farris, Stefano,Tamborini, Lucia,Molinari, Francesco,Paradisi, Francesca
supporting information, p. 3263 - 3266 (2019/06/24)
To increase the uptake of biocatalytic processes by industry, it is essential to demonstrate the reliability of enzyme-based methodologies directly applied to the production of high value products. Here, a unique, efficient, and sustainable enzymatic platform for the multi-gram synthesis of melatonin, projected to generate around 1.5 billion U.S. dollars worldwide by 2021, and its analogues was developed. The system exploits the covalent immobilization of MsAcT (transferase from Mycobacterium smegmatis) onto agarose beads increasing the robustness and longevity of the immobilized biocatalyst. The fully-automated process deriving from the integration between biocatalysis and flow chemistry is designed to maximize the overall yields (58-92%) and reduce reaction times (5 min), overcoming the limitation often associated with bioprocesses and bridging the gap between lab scale and industrial production.
Comprehensive kinetic and substrate specificity analysis of an arylsulfatase from Helix pomatia using mass spectrometry
Correia, Mário S.P.,Ballet, Caroline,Meistermann, Hannes,Conway, Louis P.,Globisch, Daniel
, p. 955 - 962 (2019/02/09)
Sulfatases hydrolyze sulfated metabolites to their corresponding alcohols and are present in all domains of life. These enzymes have found major application in metabolic investigation of drugs, doping control analysis and recently in metabolomics. Interest in sulfatases has increased due to a link between metabolic processes involving sulfated metabolites and pathophysiological conditions in humans. Herein, we present the first comprehensive substrate specificity and kinetic analysis of the most commonly used arylsulfatase extracted from the snail Helix pomatia. In the past, this enzyme has been used in the form of a crude mixture of enzymes, however, recently we have purified this sulfatase for a new application in metabolomics-driven discovery of sulfated metabolites. To evaluate the substrate specificity of this promiscuous sulfatase, we have synthesized a series of new sulfated metabolites of diverse structure and employed a mass spectrometric assay for kinetic substrate hydrolysis evaluation. Our analysis of the purified enzyme revealed that the sulfatase has a strong preference for metabolites with a bi- or tricyclic aromatic scaffold and to a lesser extent for monocyclic aromatic phenols. This metabolite library and mass spectrometric method can be applied for the characterization of other sulfatases from humans and gut microbiota to investigate their involvement in disease development.
New enzymatic and mass spectrometric methodology for the selective investigation of gut microbiota-derived metabolites
Ballet, Caroline,Correia, Mário S. P.,Conway, Louis P.,Locher, Theresa L.,Lehmann, Laura C.,Garg, Neeraj,Vujasinovic, Miroslav,Deindl, Sebastian,L?hr, J.-Matthias,Globisch, Daniel
, p. 6233 - 6239 (2018/08/07)
Gut microbiota significantly impact human physiology through metabolic interaction. Selective investigation of the co-metabolism of bacteria and their human host is a challenging task and methods for their analysis are limited. One class of metabolites associated with this co-metabolism are O-sulfated compounds. Herein, we describe the development of a new enzymatic assay for the selective mass spectrometric investigation of this phase II modification class. Analysis of human urine and fecal samples resulted in the detection of 206 sulfated metabolites, which is three times more than reported in the Human Metabolome Database. We confirmed the chemical structure of 36 sulfated metabolites including unknown and commonly reported microbiota-derived sulfated metabolites using synthesized internal standards and mass spectrometric fragmentation experiments. Our findings demonstrate that enzymatic sample pre-treatment combined with state-of-the-art metabolomics analysis represents a new and efficient strategy for the discovery of unknown microbiota-derived metabolites in human samples. Our described approach can be adapted for the targeted investigation of other metabolite classes as well as the discovery of biomarkers for diseases affected by microbiota.
