- Oxidative damage of proline residues by nitrate radicals (NO3): A kinetic and product study
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Tertiary amides, such as in N-acylated proline or N-methyl glycine residues, react rapidly with nitrate radicals (NO3) with absolute rate coefficients in the range of 4-7 × 108 M-1 s-1 in acetonitrile. The major pathway proceeds through oxidative electron transfer (ET) at nitrogen, whereas hydrogen abstraction is only a minor contributor under these conditions. However, steric hindrance at the amide, for example by alkyl side chains at the α-carbon, lowers the rate coefficient by up to 75%, indicating that NO3-induced oxidation of amide bonds proceeds through initial formation of a charge transfer complex. Furthermore, the rate of oxidative damage of proline and N-methyl glycine is significantly influenced by its position in a peptide. Thus, neighbouring peptide bonds, particularly in the N-direction, reduce the electron density at the tertiary amide, which slows down the rate of ET by up to one order of magnitude. The results from these model studies suggest that the susceptibility of proline residues in peptides to radical-induced oxidative damage should be considerably reduced, compared with the single amino acid.
- Nathanael, Joses G.,Nuske, Madison R.,Richter, Annika,White, Jonathan M.,Wille, Uta
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supporting information
p. 6949 - 6957
(2020/10/02)
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- Postsynthetic modification of bacterial peptidoglycan using bioorthogonal n-acetylcysteamine analogs and peptidoglycan o-acetyltransferase B
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Bacteria have the natural ability to install protective postsynthetic modifications onto its bacterial peptidoglycan (PG), the coat woven into bacterial cell wall. Peptidoglycan O-acetyltransferase B (PatB) catalyzes the O-acetylation of PG in Gram (-) bacteria, which AIDS in bacterial survival, as it prevents autolysins such as lysozyme from cleaving the PG. We explored the mechanistic details of PatB's acetylation function and determined that PatB has substrate specificity for bioorthgonal short N-acetyl cysteamine (SNAc) donors. A variety of functionality including azides and alkynes were installed on tri-N-acetylglucosamine (NAG)3, a PG mimic, as well as PG isolated from various Gram (+) and Gram (-) bacterial species. The bioorthogonal modifications protect the isolated PG against lysozyme degradation in vitro. We further demonstrate that this postsynthetic modification of PG can be extended to use click chemistry to fluorescently label the mature PG in whole bacterial cells of Bacillus subtilis. Modifying PG postsynthetically can aid in the development of antibiotics and immune modulators by expanding the understanding of how PG is processed by lytic enzymes.
- Wang, Yiben,Lazor, Klare M.,DeMeester, Kristen E.,Liang, Hai,Heiss, Tyler K.,Grimes, Catherine L.
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supporting information
p. 13596 - 13599
(2017/11/06)
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- Preparing method for N-acetyl-L-carnosine
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The invention discloses a preparing method for N-acetyl-L-carnosine and belongs to the technical field of medical intermediates. The method comprises the steps that beta-alanine is subjected to ammonia acetylization to obtain N-acetyl-beta-alanine; N-acetyl-beta-alanine and L-histidine are condensed to obtain N-acetyl-beta-carnosine. N-acetyl-beta-alanine and an acylation reagent react in a non-polar solvent to obtain N-acetyl-beta-alanyl chloride, and L-histidine and organosilane react under the catalyzing of acid to obtain organosilane-protected L-histidine; then organosilane-protected L-histidine and N-acetyl-beta-alanyl chloride are condensed to obtain organosilane-protected N-acetyl-L carnosine, a polar solvent is added to remove protecting groups, and N-acetyl-L-carnosine is obtained through separation and purification. Or, N-acetyl-beta-alanine and L-histidine are condensed under the action of a condensing agent to obatin N-acetyl-L-carnosine.
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Paragraph 0030
(2017/03/14)
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- Energetic contribution to both acidity and conformational stability in peptide models
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The acidity of N-acyl amino acids is dependent upon the rotameric state of the amide bond. In this work we systematically investigated the acidity difference of the rotamers (ΔpKa) in the frames of various acetylated amino acids. Our results indicated a mutual interaction of two carbonyl groups of an attractive type. We observed conservative ΔpKas for acyclic amino acids (2.2-3.0 kJ mol-1), whereas in the case of alicyclic amino acids, the experimental values revealed a strong dependency on the structural context (1.5-4.4 kJ mol-1). In homologous amino acids (α-, β-, γ-, etc.), the strength of the attraction decays in an exponential fashion. Furthermore, the interaction can accumulate through a chain of amide bonds in a cascade fashion, as demonstrated by an Ac-Pro-Pro dipeptide. As a result, we demonstrate that ΔpKa is an experimental parameter to estimate increments in the carbonyl-carbonyl alignment, as determined by the amino acid or peptidyl context. This parameter is also important in understanding the roles of amino acids in both protein folding and translation in biological systems as well as their evolutionary appearance in the genetic code.
- Kubyshkin, Vladimir,Durkin, Patrick,Budisa, Nediljko
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supporting information
p. 5209 - 5220
(2016/07/06)
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- Direct C-H alkylation of naphthoquinones with amino acids through a revisited Kochi-Anderson radical decarboxylation: Trends in reactivity and applications
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In our ongoing research program into the discovery of new anticancer drugs, we were interested in the preparation of naphthoquinone scaffolds bearing aminoalkyl side-chains. Following this aim, we revisited the Kochi-Anderson radical decarboxylation of amino acids in order to set up a versatile route to the direct functionalization of naphthoquinones. The best reaction conditions were applied to a selected series of compounds in a systematic methodological study which allowed us to establish important trends in reactivity. We found that α-substituted β-amino acids were the most suitable substrates for the radical addition. In contrast, α-amino acids gave modest results. The influence of the amine protecting groups on the reaction outcome has also been studied. This practical procedure allows the introduction of various unsymmetrical moieties, including orthogonally protected linear aminoalkyl chains or chiral dipeptidic chains, and opens the door to a wide scope of easily accessible chemical diversity.
- Naturale, Guillaume,Lamblin, Marc,Commandeur, Claude,Dessolin, Jean,Felpin, Francois-Xavier
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supporting information
p. 5774 - 5788,15
(2020/09/15)
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- PROCESS FOR STRAIGHTENING KERATIN FIBRES WITH A HEATING MEANS AND DENATURING AGENTS
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The invention relates to a process for straightening keratin fibres, comprising: (i) a step in which a straightening composition containing at least two denaturing agents is applied to the keratin fibres, (ii) a step in which the temperature of the keratin fibres is raised, using a heating means, to a temperature of between 110 and 250° C.
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- Nucleoside derivatives for library preparation
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Nucleoside derivatives as building blocks for templated libraries are described.
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- Functionalized DL-Amino Acid Derivatives. Potent New Agents for the Treatment of Epilepsy
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Structural analogues of the potent known anticonvulsant agent N-acetyl-DL-alanine N-benzylamide (1a) have been prepared (16 examples).The pharmacological activities of these products were evaluated in the maximal electroshock seizure (MES), the subcutaneous pentylenetetrazole seizure threshold (sc Met), and the rotorod (Tox) tests.The median effective doses (ED50) and the median toxic doses (TD50) for the most active compounds by both intraperitoneal and oral administration are reported.The most active compounds were N-acetyl-DL-phenylglycine N-benzylamide (1d) and N-acetyl-DL-alanine N-m-fluorobenzylamide (1m) along with the parent compound 1a.The ED50 values in the MES test for these three compounds compared well with phenobarbital, while their high TD50 values contributed to their large protective indexes, which approached that of phenytoin.When tested against four convulsant agents, compounds 1a and 1d displayed activity profiles significantly different from those reported for conventionally used antiepileptic drugs.
- Conley, Judith D.,Kohn, Harold
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p. 567 - 574
(2007/10/02)
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- Comparison of the hypolipidemic activity of cyclic vs. acyclic imides
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Two series of nitrogen-substituted cyclic and acyclic imides were examined for hypolipidemic activity in mice after dosing for 16 days at a dose of 20 mg/kg per day. The hypolipidemic activity of the unsubstituted, N-butyl, N-3-oxobutyl, and N-2-carboxyethyl derivatives of diacetimide and succinimide were compared as well as the unsubstituted and N-substituted dibenzimide and diphenimide. It was shown that an imide functionally incorporated into a ring was not necessary for hypocholesterolemic activity. Good hypocholesterolemic activity was observed in both series of acyclic and cyclic imides. However, a cyclic imido structure was a necessary requirement for good hypotriglyceridemic activity. A decrease in hypotriglyceridemic activity was noted when comparing the cyclic imides to their respective acyclic congeners.
- Voorstad,Chapman,Cocolas,Wyrick,Hall
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