197891-66-0Relevant articles and documents
Unexpected Acetylation of Endogenous Aliphatic Amines by Arylamine N-Acetyltransferase NAT2
Bergdahl, Ingvar A.,Conway, Louis P.,Correia, Mário S. P.,Globisch, Daniel,Rendo, Veronica,Sj?blom, Tobias
, p. 14342 - 14346 (2020)
N-Acetyltransferases play critical roles in the deactivation and clearance of xenobiotics, including clinical drugs. NAT2 has been classified as an arylamine N-acetyltransferase that mainly converts aromatic amines, hydroxylamines, and hydrazines. Herein, we demonstrate that the human arylamine N-acetyltransferase NAT2 also acetylates aliphatic endogenous amines. Metabolomic analysis and chemical synthesis revealed increased intracellular concentrations of mono- and diacetylated spermidine in human cell lines expressing the rapid compared to the slow acetylator NAT2 phenotype. The regioselective N8-acetylation of monoacetylated spermidine by NAT2 answers the long-standing question of the source of diacetylspermidine. We also identified selective acetylation of structurally diverse alkylamine-containing drugs by NAT2, which may contribute to variations in patient responses. The results demonstrate a previously unknown functionality and potential regulatory role for NAT2, and we suggest that this enzyme should be considered for re-classification.
COMPOUNDS AND COMPOSITIONS FOR INTRACELLULAR DELIVERY OF THERAPEUTIC AGENTS
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Paragraph 00295, (2018/10/19)
The disclosure features novel lipids and compositions involving the same. Nanoparticle compositions include a novel lipid as well as additional lipids such as phospholipids, structural lipids, and PEG lipids. Nanoparticle compositions further including therapeutic and/or prophylactics such as RNA are useful in the delivery of therapeutic and/or prophylactics to mammalian cells or organs to, for example, regulate polypeptide, protein, or gene expression.
Design, synthesis and SAR studies of GABA uptake inhibitors derived from 2-substituted pyrrolidine-2-yl-acetic acids
Steffan, Tobias,Renukappa-Gutke, Thejavathi,H?fner, Georg,Wanner, Klaus T.
, p. 1284 - 1306 (2015/03/04)
In this paper, we disclose the design and synthesis of a series of 2-substituted pyrrolidine-2-yl-acetic acid as core structures and the N-arylalkyl derivatives thereof as potential GABA transport inhibitors. The 2-position in the side chain of pyrrolidin
Dihydroxylation of vinyl sulfones: Stereoselective synthesis of (+)- and (-)-febrifugine and halofuginone
McLaughlin, Noel P.,Evans, Paul
supporting information; experimental part, p. 518 - 521 (2010/03/30)
(Chemical Equation Presented) The asymmetric dihydroxylation of amino-functionalized vinyl sulfone 19 has been used for the 3-step preparation of 3-hydroxylpiperidine 24 in 86% enantiomeric excess. This enantiomerically enriched building block was used then to synthesize the naturally occurring antimalarial alkaloid febrifugine 1 and its antiangiogenic analogue, halofuginone 3.
Microbial Baeyer-Villiger oxidation applied to the synthesis of the N-protected (1R,5R)-Geisman-Waiss lactone
Luna, Amparo,Gutierrez, Maria-Concepcion,Furstoss, Roland,Alphand, Veronique
, p. 2521 - 2524 (2007/10/03)
Using whole cell Baeyer-Villiger biooxidation as a key step and depending on the choice of the biocatalyst {E. coli TOP10[pQR239] or Acinetobacter TD63}, the synthesis of nearly enantiopure N-protected (1R,5R)-(-)-Geisman-Waiss lactone (92% ee) or its (1R
Synthesis of (+/-) - oxohexahydrofuro[3,2-b]pyrroles (pyrrolidine-trans-lactones) using acyl-iminium chemistry
Macdonald, Simon J.F.,Spooner, Julie E.,Dowle, Michael D.
, p. 1375 - 1377 (2007/10/03)
In a new synthesis of pyrrolidine-trans-lactones, an acyliminium pyrrolidine reacts with silyl ketene acetals. This reaction selectively generates C2, C3 trans stereochemistry.
