- Deciphering Carbamoylpolyoxamic Acid Biosynthesis Reveals Unusual Acetylation Cycle Associated with Tandem Reduction and Sequential Hydroxylation
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Polyoxin, produced by Streptomcyes cacaoi var. asoensis and Streptomyces aureochromogenes, contains two non-proteinogenic amino acids, carbamoylpolyoxamic acid (CPOAA) and polyoximic acid. Although the CPOAA moiety is highly unusual, its biosynthetic logic has remained enigmatic for decades. Here, we address CPOAA biosynthesis by reconstitution of its pathway. We demonstrated that its biosynthesis is initiated by a versatile N-acetyltransferase, PolN, catalyzing L-glutamate (1) to N-acetyl glutamate (2). Remarkably, we verified that PolM, a previously annotated dehydrogenase, catalyzes an unprecedented tandem reduction of acyl-phosphate to aldehyde, and subsequently to alcohol. We also unveiled a distinctive acetylation cycle catalyzed by PolN to synthesize α-amino-δ-hydroxyvaleric acid (6). Finally, we report that PolL is capable of converting a rare sequential hydroxylation of α-amino-δ-carbamoylhydroxyvaleric acid (7) to CPOAA. PolL represents an intriguing family of Fe(II)-dependent α-ketoglutarate dioxygenase with a cupin fold. These data illustrate several novel enzymatic reactions, and also set a foundation for rational pathway engineering for polyoxin production.
- Qi, Jianzhao,Wan, Dan,Ma, Hongmin,Liu, Yuanzhen,Gong, Rong,Qu, Xudong,Sun, Yuhui,Deng, Zixin,Chen, Wenqing
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- Reactions of substituted aspirins with amino acids
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Acyl transfers are key reactions in biology and in the laboratory. In biological systems they are involved in energy transport, in the assembly of complex molecules and in the mechanisms of efficient action of many hydrolytic enzymes. We report a mechanistic and calculational study of the selective N-acylation reactions of amino acids by substituted aspirins, under mild conditions, in water at 25 °C. The acetylated amino-acid products of the reactions were identified by nuclear magnetic resonance, and the reaction steps were studied by density functional theory. Copyright
- Orth, Elisa S.,Medeiros, Michelle,Souza, Bruno S.,Caon, Natalia B.,Kirby, Anthony J.,Nome, Faruk
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- New method of synthesis of D,L-5-oxoproline
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A new method for synthesis of D,L-5-oxoproline from N-acetyl-L-glutamic acid in weakly acid medium in the presence of water, and hydrolysis of an acetyl group and cyclization and total racemization of the acid simultaneously take place.The advantage of the method is the possibility of obtaining two individual amino acids with high yields in one chemical process using L-glutamic acid.
- Ermakova, G. A.,Skachilovw, S. Ya.,Yurchenko, N. I.
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- Oxidative Damage in Aliphatic Amino Acids and Di- and Tripeptides by the Environmental Free Radical Oxidant NO3?: the Role of the Amide Bond Revealed by Kinetic and Computational Studies
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Kinetic and computational data reveal a complex behavior of the important environmental free radical oxidant NO3? in its reactions with aliphatic amino acids and di- and tripeptides, suggesting that attack at the amide N-H bond in the peptide backbone is a highly viable pathway, which proceeds through a proton-coupled electron transfer (PCET) mechanism with a rate coefficient of about 1 × 106 M-1 s-1 in acetonitrile. Similar rate coefficients were determined for hydrogen abstraction from the α-carbon and from tertiary C-H bonds in the side chain. The obtained rate coefficients for the reaction of NO3? with aliphatic di- and tripeptides suggest that attack occurs at all of these sites in each individual amino acid residue, which makes aliphatic peptide sequences highly vulnerable to NO3?-induced oxidative damage. No evidence for amide neighboring group effects, which have previously been found to facilitate radical-induced side-chain damage in phenylalanine, was found for the reaction of NO3? with side chains in aliphatic peptides.
- Nathanael, Joses G.,Wille, Uta
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p. 3405 - 3418
(2019/03/11)
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- Peptide Tyrosinase Activators
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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.
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- Synthesis, characterisation, and biological activity of three new amide prodrugs of lamotrigine with reduced hepatotoxicity
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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.
- Sinha, Saurabh K.,Shrivastava, Prabhat K.,Shrivastava, Sushant K.
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experimental part
p. 70 - 76
(2011/12/21)
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- Peculiar stability of amino acids and peptides from a radical perspective
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(Chemical Equation Presented) Photochemical reactions of free and N-acetyl α-amino acids with chlorine and deuterium labeled hydrogen peroxide have been used to determine both the relative rates of reaction of molecules of these classes and the relative reactivity of their different types of hydrogen toward abstraction by chlorine and oxygen centered radicals. The relative rates of reaction of these species range over more than 3 orders of magnitude; however, where data are available from more than one amino acid for a particular type of group at a specific position on the side chain, the values are remarkably similar. The predictive utility of these results has been demonstrated for the regioselective chlorination of tripeptides. More generally this analysis shows that the backbone and adjacent side chain positions of amino acids and peptides are peculiarly resistant to hydrogen atom transfer, and a similar pattern of reactivity has been noted from earlier studies of reactions of modified substrates catalyzed by isopenicillin-N-synthetase. Such resistance stands out in contrast to the common occurrence of free radical reactions of α-amino acids, peptides, and proteins and their importance in biology. Nevertheless, it provides a reason for the ability of amino acids and their derivatives to avoid degradation in Nature where they are constantly exposed to radicals, and it accounts, at least in part, for the anomalous ability of enzymes to catalyze free radical reactions without being broken down by the radical intermediates.
- Watts, Zachary I.,Easton, Christopher J.
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supporting information; experimental part
p. 11323 - 11325
(2011/03/19)
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- Cosmetic composition
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A composition suitable for topical application to mammalian skin and hair for inducing, maintaining or increasing hair growth comprises a hair growth promoter chosen from glutamine derivatives and salts thereof. The composition preferably also comprises an activity enhancer which may be chosen from hair growth stimulants, penetration enhancers and cationic polymers.
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- Cosmetic composition containing DOPA derivatives
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A composition for topical application to human hair or skin contains a chemical analogue of dihydroxyphenyl alanine (DOPA). This chemical analogue can be absorbed by skin or by a hair follicle and metabolised in-vivo, thus leading to the formation of melanin in skin or to the growth of melanin-pigmented hair. Consequently the composition can give controlled skin darkening to mimic sun-induced tanning or can bring about the growth of dar hair in place of the grey or white hair.
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- Cosmestic composition
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A composition suitable for topical application to mammalian skin and hair for inducing, maintaining or increasing hair growth comprises a hair growth promoter chosen from glutamic acid derivatives and salts thereof. The composition preferably also comprises an activity enhancer which may be chosen from hair growth stimulants, penetration enhancers and cationic polymers.
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- RENAL-SELECTIVE BIPHENYLALKYL 1H-SUBSTITUTED-1,2,4-TRIAZOLE ANGIOTENSIN II ANTAGONISTS FOR TREATMENT OF HYPERTENSION
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Renal-selective compounds are described which, in one embodiment, are prodrugs preferentially converted in the kidney to compounds capable of blocking angiotensin II (AII) receptors. These prodrugs are conjugates formed from two components, namely, a first component provided by an AII antagonist compound and a second component which is capable of being cleaved from the first component when both components are chemically linked within the conjugate. The two components are chemically linked by a bond which is cleaved selectively in the kidney, for example, by an enzyme. The liberated AII antagonist compound is then available to block AII receptors within the kidney. Conjugates of particular interest are glutamyl derivatives of biphenylmethyl 1H-substituted-1,2,4-triazole compounds, of which N-acetylglutamic acid, 5-[[4'-[(3,5-dibutyl-1H-1,2,4-triazol-1-yl)methyl][1,1'-biphenyl]-2-yl]] car bonylhydrazide, (shown below) is an example: STR1
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- Hair growth composition containing citric acid esters
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Triesters of citric acid are used for inducing, maintaining or increasing hair growth. Compositions for topical application to mammalian hair or scalp comprise an effective amount of from 1% to 99% by weight of an ester of citric acid having the structure (1): where, R1, R2 and R3 each independently represent a branched or unbranched alkyl, alkenyl, aryl, alkylaryl or arylalkyl group, each said group having from 1 to 18 carbon atoms, R4 represents -H, or a branched or unbranched saturated or unsaturated acyl, alkyl, aryl, alkylaryl or aylalkyl group having from 1 to 18 carbon atoms, in the presence of a cosmetically acceptable vehicle for the citric acid ester and in the absence of solid absorbent for the ester;, said effective amount of said ester being sufficient to increase hair growth in the rat, when said composition is applied topically thereto over a period of no more than three months, by at least 10% more than that obtainable using a control composition from which the said ester has been omitted, in accordance with the Rat Hair Growth Test.
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- Acetylation under ultrasonic conditions: Convenient preparation of N-acetylamino acids
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An efficient and simple method of preparation of acetylamino acids from amino acids under ultrasonic conditions is described. The reactions proceed without racemization and the yields are almost quantitative.
- Veera Reddy,Ravindranath
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p. 257 - 264
(2007/10/02)
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- Cosmetic composition
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A composition suitable for topical application to mammalian skin and hair for inducing, maintaining or increasing hair growth comprises a hair growth promoter chosen from N-acylated amino-acids, in which the acyl group has from 2 to 20 carbon atoms, together with a cosmetically acceptable vehicle for the hair growth promoter.
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