877036-29-8Relevant articles and documents
A the graciousness favorable card lives synthetic method
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Paragraph 0040, (2017/08/03)
A synthetic method for emricasan belongs to the technical field of drug chemical synthesis. The synthetic method comprises the steps: firstly carrying out acyl chlorination reaction on pyruvic acid and an acyl chlorination reagent to obtain pyruvoyl chlor
Assays, methods and means
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, (2010/12/26)
A novel class of hydroxylases is described having the amino acid sequence of SEQ ID NO: 2, 4, 6 and 8, and variants and fragments thereof having HIF hydroxylation activity. The polypeptides of the invention have in particular prolyl hydroxylase activity. An assay method monitors the interaction of the HIF hydroxylase with a substrate. Modulators of HIF hydroxylase are provided for use in the treatment of a condition associated with increased or decreased HIF levels or activity or for the treatment of a condition where it is desirable to modulate HIF levels or activity.
Intracellular oxidation of dipeptides. Base-promoted elimination from N-halodipeptides to 2-[N-alkyl-N-(2-N- alkylimino-2-alkyl-ethanoyl)amino]-2,2-dialkylethanoic acids
Armesto,Canle,Fernandez,Garci,Rodriguez,Santaballa
, p. 5692 - 5700 (2007/10/03)
One of the possible ways of intracellular oxidation of peptides is via the formation of the corresponding (N-X)-dipeptides, that then undergo base-promoted elimination to yield intermediate 2-[N-alkyl-N-(2-N-alkylimino-2-alkylethanoyl)amino]-2,2-dialkylethanoic acids, which subsequently hydrolyze. Such an elimination process is general-base catalyzed, with Bronsted β values ranging from 0.26 to 0.31, which suggests an essentially constant degree of proton transfer at the TS. For (N-X)-dipeptides, the ratio kN-Br/kN-Cl ranges from 2.5 to 15, suggesting a structural dependence of the degree of N-X bond breaking at the TS. The values of β and kN-Br/kN-Cl support a concerted asynchronous AxhDHDN mechanism, its TS changing from reactant-like to slightly nitrenium-like depending on the structure of the starting dipeptide. As a consequence of the antiperiplanarity requirements of the reaction, the steric interaction between the leaving group and the substituent on the C bearing the H to be eliminated controls the reaction rate. Such steric interaction is rather important, as indicated by the steric crossed-interaction coefficient (pssy = 0.33). Semiempirical calculations show that bulky substituents in the vicinity of the reaction center imply additional energy requirements for the system to achieve the antiperiplanarity needed at the TS for the reaction to proceed. From the observations reported it follows that (N-X)-dipeptides lose their oxidizing power more readily than analogous (N-X)-amino acids or (N-X)-amines, opening a possible pathway to lessen intracellular halogen-based oxidative stress.
Pyridoxal-catalyzed release of nucleotides
Pochet, Sylvie,Beaussire, Jean-Jacques,Dugue, Laurence,Marliere, Philippe
, p. 1019 - 1020 (2007/10/03)
The synthesis of phosphoric esters linking the 5' alcohol of thymidine to the alcohol moiety of L-serine derivatives is reported, together with the pyridoxal-catalyzed β-elimination reaction releasing thymidylate from such compounds. The process was extended to the release of thymidine di- and tri- phosphate.
