- Subtype-Specific Agonists for NMDA Receptor Glycine Binding Sites
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A series of analogues based on serine as lead structure were designed, and their agonist activities were evaluated at recombinant NMDA receptor subtypes (GluN1/2A-D) using two-electrode voltage-clamp (TEVC) electrophysiology. Pronounced variation in subunit-selectivity, potency, and agonist efficacy was observed in a manner that was dependent on the GluN2 subunit in the NMDA receptor. In particular, compounds 15a and 16a are potent GluN2C-specific superagonists at the GluN1 subunit with agonist efficacies of 398% and 308% compared to glycine. This study demonstrates that subunit-selectivity among glycine site NMDA receptor agonists can be achieved and suggests that glycine-site agonists can be developed as pharmacological tool compounds to study GluN2C-specific effects in NMDA receptor-mediated neurotransmission.
- Maolanon, Alex R.,Risgaard, Rune,Wang, Shuang-Yan,Snoep, Yoran,Papangelis, Athanasios,Yi, Feng,Holley, David,Barslund, Anne F.,Svenstrup, Niels,Hansen, Kasper B.,Clausen, Rasmus P.
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p. 1681 - 1687
(2017/08/21)
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- Efficient S-alkylation of cysteine in the presence of 1,1,3,3- tetramethylguanidine
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The synthesis of S-alkylated cysteine derivatives was carried out successfully in the presence of 1,1,3,3-tetramethylguanidine. Alkylation proceeded in high yields on unprotected amino acids and peptides containing a sulfhydryl group.
- W?ostowski, Marek,Czarnocka, Sylwia,MacIejewski, Piotr
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experimental part
p. 5977 - 5979
(2010/11/21)
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- Method Of Synthesizing S-Allyl-Cysteine Analogues And Their Therapeutic Application In Treating Myocardial Infarction
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A pharmaceutical composition and methods of producing and application of the composition for treating myocardial infarction of a subject are disclosed. The pharmaceutical composition comprises a therapeutically effective amount of at least one synthesized compound selected from the group consisting of SEC, SPC, SBC, SPEC, SAC, SAMC, and SPRC, and a pharmaceutically acceptable carrier.
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Page/Page column 10
(2009/04/24)
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- ALPHA-HELICAL MIMETICS
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Benzoyl urea derivatives that are alpha helical peptide mimetics that mimic BH3-only proteins, compositions containing them, their conjugation to cell-targeting moieties, and their use in the regulation of cell death are disclosed. The benzoyl urea derivatives are capable of binding to and neutralising pro-survival Bcl-2 proteins. Use of the benzoyl urea derivatives in the treatment and/or prophylaxis of diseases or conditions associated with deregulation of cell death are also disclosed.
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Page/Page column 206
(2010/02/15)
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- Asymmetric synthesis of S-alkyl-substituted (R)-cysteines via a chiral NiII complex of the Schiff's base of dehydroalanine with (S)-2-N-(N-benzylprolyl)aminobenzophenone
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An efficient procedure was developed for the asymmetric synthesis of S-alkyl derivatives of (R)-cysteine by nucleophilic addition of alkanethiols (BunSH, ButSH, or tert-C5H11SH) to the C=C bond of the dehydroalanine fragment in the Ni11 complex of the Schiff's base of Δ-Ala with (S)-2-N-(N-benzylprolyl)aminobenzophenone [(S)-BPB-Δ-Ala]Ni11. Under conditions of thermodynamic control of the reaction, the diastereomeric excess of the complexes with the (S,R)-configuration was 88 - 96%. After decomposition of the complexes, (R)-S-butylcysteine, (R)-S-tert-butylcysteine, and (R)-S-tert-pentylcysteine were isolated with an enantiomeric purity of >97%.
- Saghiyan,Geolchanyan,Djamgaryan,Vardapetyan,Tararov,Kuz'mina,Ikonnikov,Belokon',North
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p. 1460 - 1463
(2007/10/03)
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- Acylase I-catalyzed deacetylation of N-acetyl-L-cysteine and S-alkyl-N- acetyl-L-cysteines
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The aminoacylase that catalyzes the hydrolysis of N-acetyl-L-cysteine (NAC) was identified as acylase I after purification by column chromatography and electrophoretic analysis. Rat kidney cytosol was fractionated by ammonium sulfate precipitation, and the proteins were separated by ion-exchange column chromatography, gel-filtration column chromatography, and hydrophobic interaction column chromatography. Acylase activity with NAC and N-acetyl-L- methionine (NAM), a known substrate for acylase I, as substrates coeluted during all chromatographic steps. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed that the protein was purified to near homogeneity and had a subunit M(r) of 43 000, which is identical with the M(r) of acylase I from porcine kidney and bovine liver. n-Butylmalonic acid was a slow-binding inhibitor of acylase I and inhibited the deacetylation of NAC with a K(i) of 192 ± 27 μM. These results show that acylase I catalyzes the deacetylation of NAC. The acylase I-catalyzed deacetylation of a range of S-alkyl-N- acetyl-L-cysteines, their carbon and oxygen analogues, and the selenium analogue of NAM was also studied with porcine kidney acylase I. The specific activity of the acylase I-catalyzed deacetylation of these substrates was related to their calculated molar volumes and log P values. The S-alkyl-N- acetyl-L-cysteines with short (C0-C3) and unbranched S-alkyl substituents were good acylase I substrates, whereas the S-alkyl-N-acetyl-L-cysteines with long (>C3) and branched S-alkyl substituents were poor acylase I substrates. The carbon and oxygen analogues of S-methyl-N-acetyl-L-cysteine and the carbon analogue of S-ethyl-N-acetyl-L-cysteine were poor acylase I substrates, whereas the selenium analogue of NAM was a good acylase I substrate.
- Uttamsing, Vinita,Keller,Anders
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p. 800 - 809
(2007/10/03)
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