65-82-7Relevant articles and documents
Structure-activity relationship studies of dipeptide-based hepsin inhibitors with Arg bioisosteres
Kwon, Hongmok,Ha, Hyunsoo,Jeon, Hayoung,Jang, Jaebong,Son, Sang-Hyun,Lee, Kiho,Park, Song-Kyu,Byun, Youngjoo
supporting information, (2020/12/25)
Hepsin is a type II transmembrane serine protease (TTSP) associated with cell proliferation and overexpressed in several types of cancer including prostate cancer (PCa). Because of its significant role in cancer progression and metastasis, hepsin is an attractive protein as a potential therapeutic and diagnostic biomarker for PCa. Based on the reported Leu-Arg dipeptide-based hepsin inhibitors, we performed structural modification and determined in vitro hepsin- and matriptase-inhibitory activities. Comprehensive structure-activity relationship studies identified that the p-guanidinophenylalanine-based dipeptide analog 22a exhibited a strong hepsin-inhibitory activity (Ki = 50.5 nM) and 22-fold hepsin selectivity over matriptase. Compound 22a could be a prototype molecule for structural optimization of dipeptide-based hepsin inhibitors.
Bio- And Medicinally Compatible α-Amino-Acid Modification via Merging Photoredox and N-Heterocyclic Carbene Catalysis
Chen, Lei,Du, Ding,Feng, Jie,Gao, Jian,Lu, Tao,Ma, Rui,Shi, Zhihao,Zhang, Kuili
supporting information, (2020/09/02)
An N-heterocyclic carbene and photoredox cocatalyzed α-amino-acid decarboxylative carbonylation reaction is presented. This method displays good scope generality, providing a direct pathway to access various downstream α-amino ketones under bio- and medicinally compatible conditions. Moreover, this strategy is appealing to chemical biology because it has great potential for the chemical modification of peptides or the late-stage synthesis of keto-peptides.
Synthesis method of (2S)-2-(acetamino)-4-(methylsulfinyl)butyric acid
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Paragraph 0019, (2019/01/08)
The invention relates to a synthesis method of (2S)-2-(acetamino)-4-(methylsulfinyl)butyric acid and mainly aims to solve the technical problems of high cost, high pollution, numerous by-products andharm to mass production of the existing synthesis method. The method comprises the following steps: (1) dissolving solid L-methionine in a sodium carbonate aqueous solution, dropwise adding liquid acetic anhydride, stirring for reacting, filtering and washing unreacted acetic anhydride in filtrate by using a mixed solution of ethyl acetate and petroleum ether, adding an extraction agent which is ethyl acetate into a water phase, acidizing by using solid citric acid, layering, washing, drying and carrying out reduced-pressure distillation to obtain an intermediate which is Nalpha-acetyl-L-methionine; and (2) dissolving the intermediate which is Nalpha-acetyl-L-methionine in acetic acid, dropwise adding hydrogen peroxide with mass percentage concentration of 30%, stirring for reacting, concentrating an obtained product till the product is dry, adding alcohol and crystallizing to obtain the product which is (2S)-2-(acetamino)-4-(methylsulfinyl)butyric acid. The (2S)-2-(acetamino)-4-(methylsulfinyl) butyric acid is used as a raw material for synthesizing a polypeptide drug.
Synthesis, spectroscopic and X-ray characterization of various pyrazine-bridged platinum(II) complexes:1H NMR comparative study of their catalytic abilities in the hydrolysis of methionine- and histidine-containing dipeptides
Rajkovi?, Sne?ana,?ivkovi?, Marija D.,Warzajtis, Beata,Rychlewska, Urszula,Djuran, Milo? I.
, p. 367 - 376 (2016/07/06)
Four pyrazine (pz)-bridged Pt(II) complexes, [{Pt(1,3-pd)Cl}2(μ-pz)]Cl2·LiCl (1) (1,3-pd = 1,3-propylenediamine), [{Pt(2,2-diMe-1,3-pd)Cl}2(μ-pz)]Cl2·2[Li(H2O)4]Cl·2H2O (2) (2,2-diMe-1,3-pd = 2,2-dimethyl-1,3-propylenediamine), [{Pt(1,3-pnd)Cl}2(μ-pz)](ClO4)2·H2O (3) (1,3-pnd = (±)-1,3-pentanediamine) and [{Pt(1,3-pnd)Cl}2(μ-pz)]Cl2·2[Pt(1,3-pnd)Cl2]·2H2O (4) have been synthesized. NMR and UV-Vis spectroscopic characterization has been performed for compounds 1-3, while single-crystal X-ray analysis has been carried out for complexes 2 and 4. Atomic distribution in the crystals of 4 indicated a disorder which could be attributed to the presence at the same crystallographic site of four distinct stereoisomers of the [{Pt(1,3-pnd)Cl}2(μ-pz)]2+complex cation. The presence of four stereoisomeric products was also observed in complex 3 by13C NMR spectroscopy. Complexes 1-3 were converted into the corresponding aqua complexes, [{Pt(X)(H2O)}2(μ-pz)]4+(X is 1,3-pd, 2,2-diMe-1,3-pd and 1,3-pnd, respectively), and1H NMR spectroscopy was applied for comparison of their catalytic activities with those of the analogous mononuclear [Pt(X)(H2O)2]2+and pyrazine-bridged [{Pt(en)(H2O)}2(μ-pz)]4+complexes in the hydrolysis of the N-acetylated l-methionylglycine (Ac-l-Met-Gly) and l-histidylglycine (Ac-l-His-Gly). All reactions were performed in the pH range 2.0-2.5 at 37 °C. It was found that all investigated dinuclear Pt(II)-aqua complexes promote selective cleavage of the amide bond involving carboxylic group of the anchoring amino acid methionine in the Ac-l-Met-Gly or histidine in the Ac-l-His-Gly.1H NMR data indicate that neither the size of the chelated diamine ring (five-membered in ethylenediamine and six-membered in 1,3-propylenediamine) nor the bulky substituents incorporated into the 1,3-propylenediamine ligand have significant influence on the rate of hydrolysis of Ac-l-Met-Gly dipeptide. Meanwhile, the rate of hydrolysis of Ac-l-His-Gly depends on both of these factors and decreases in order en > 1,3-pd > 1,3-pnd > 2,2-diMe-1,3-pd. Moreover, it has been shown that all investigated dinuclear Pt(II)-aqua complexes are better catalytic agents in the hydrolysis of the dipeptides than the analogous mononuclear Pt(II)-aqua complexes. The present findings are expected to play a crucial role in the development of new Pt(II) complexes, which can act as effective catalytic reagents for the selective hydrolysis of peptides containing either methionine or histidine residues.
Peptide Tyrosinase Activators
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, (2015/06/10)
Peptides that increase melanin synthesis are provided. These peptides include pentapeptides YSSWY, YRSRK, and their variants. The peptides may activate the enzymatic activity of tyrosinase to increase melanin synthesis. The pharmaceutical, cosmetic, and other compositions including the peptides are also provided. The methods of increasing melanin production in epidermis of a subject are provided where the methods include administering compositions comprising an amount of one or more peptides effective to increase the melanin production. The methods also include treating vitiligo or other hypopigmentation disorders with compositions including one or more peptides.
A detailed study of antibacterial 3-acyltetramic acids and 3-acylpiperidine-2,4-diones
Jeong, Yong-Chul,Bikadi, Zsolt,Hazai, Eszter,Moloney, Mark G.
supporting information, p. 1826 - 1837 (2014/08/18)
Inspired by the core fragment of antibacterial natural products such as streptolydigin, 3-acyltetramic acids and 3-acylpiperidine-2,4-diones have been synthesised from the core heterocycle by direct acylation with the substituted carboxylic acids using a strategy which permits ready access to a structurally diverse compound library. The antibacterial activity of these systems has been established against a panel of Gram-positive and Gram-negative bacteria, with activity mostly against the former, which in some cases is very potent. Data consistent with modes of action against undecaprenylpyrophosphate synthase (UPPS) and/or RNA polymerase (RNAP) for a small subset of the library has been obtained. The most active compounds have been shown to exhibit binding at known binding sites of streptolydigin and myxopyronin at UPPS and RNAP. These systems offer potential for their antibacterial activity, and further demonstrate the use of natural products as biologically validated starting points for drug discovery.
PROCESS FOR PRODUCING N-ACYL AMINO ACIDS
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Paragraph 0030, (2013/05/21)
An object of the present invention is to provide a process for producing an N-acyl amino acid (1) in a good yield. The present invention provides a process for producing an N-acyl amino acid (1) by reacting an aldehyde compound (2), an amide compound (3), and carbon monoxide in the solvent in a reactor in the presence of a cobalt compound and hydrogen, characterized in the aldehyde compound (2), the amide compound (3) and the solvent are supplied to the reactor in which the solvent, the cobalt compound, hydrogen and carbon monoxide have been placed in advance.
An improved racemase/acylase biotransformation for the preparation of enantiomerically pure amino acids
Baxter, Scott,Royer, Sylvain,Grogan, Gideon,Brown, Fraser,Holt-Tiffin, Karen E.,Taylor, Ian N.,Fotheringham, Ian G.,Campopiano, Dominic J.
supporting information, p. 19310 - 19313 (2013/02/23)
Using directed evolution, a variant N-acetyl amino acid racemase (NAAAR G291D/F323Y) has been developed with up to 6-fold higher activity than the wild-type on a range of N-acetylated amino acids. The variant has been coupled with an enantiospecific acylase to give a preparative scale dynamic kinetic resolution which allows 98% conversion of N-acetyl-dl-allylglycine into d-allylglycine in 18 h at high substrate concentrations (50 g L-1). This is the first example of NAAAR operating under conditions which would allow it to be successfully used on an industrial scale for the production of enantiomerically pure α-amino acids. X-ray crystal analysis of the improved NAAAR variant allowed a comparison with the wild-type enzyme. We postulate that a network of novel interactions that result from the introduction of the two side chains is the source of improved catalytic performance.
METHOD FOR PRODUCING N-ACYLAMINO ACID
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Page/Page column 4, (2012/10/08)
There is provided a method for producing N-acylamino acid of formula (I): wherein R1, R2 and R3 are the same or different and each independently represents a hydrogen atom, a substituted or unsubstituted hydrocarbyl group, or a substituted or unsubstituted heterocyclic group, which comprises supplying an aldehyde compound of formula (II): wherein R1 is as defined above, an amide compound of formula (III): wherein R2 and R3 are as defined above, and a solvent to a reactor in which a solvent, a palladium compound, a halide compound, and carbon monoxide had been charged.
Synthesis, characterisation, and biological activity of three new amide prodrugs of lamotrigine with reduced hepatotoxicity
Sinha, Saurabh K.,Shrivastava, Prabhat K.,Shrivastava, Sushant K.
experimental part, p. 70 - 76 (2011/12/21)
Lamotrigine (LTG) is an antiepileptic drug used for the prevention of convulsions. Except several known side effects, hepatic dysfunction is also reported. Hepatotoxic side effects occur due to the dichlorophenyl moiety which develops an abnormally low level of glutathione. Depletion of glutathione causes oxidative stress and hepatic cell damage. The goal of the present study was to test the action and side effects of the three compounds synthesised and compared to LTG. Three amide prodrugs of LTG were synthesised by its reaction with N-acetylamino acids, viz, glycine, glutamic acid, and methionine. Purified synthesised prodrugs were subjected to thin layer chromatography, melting point, solubility and partition coefficients determination and characterised by UV, FTIR, 1H and 13C NMR spectroscopy. The synthesised prodrugs were subjected to in vitro hydrolysis and to anticonvulsant and hepatotoxic activity studies. Significant reduction in hepatotoxicity and comparable anticonvulsant activities were obtained in all synthesised prodrugs as compared to LTG.
