134933-17-8Relevant articles and documents
Identification of an isoform catalyzing the CoA conjugation of nonsteroidal anti-inflammatory drugs and the evaluation of the expression levels of acyl-CoA synthetases in the human liver
Hashizume, Hiroki,Fukami, Tatsuki,Mishima, Kanji,Arakawa, Hiroshi,Mishiro, Kenji,Zhang, Yongjie,Nakano, Masataka,Nakajima, Miki
, (2020/11/05)
Nonsteroidal anti-inflammatory drugs (NSAIDs) containing carboxylic acid are conjugated with coenzyme A (CoA) or glucuronic acid in the body. It has been suggested that these conjugates are associated with toxicities, such as liver injury and anaphylaxis,
A versatile biosynthetic approach to amide bond formation
Philpott, Helena K.,Thomas, Pamela J.,Tew, David,Fuerst, Doug E.,Lovelock, Sarah L.
supporting information, p. 3426 - 3431 (2018/08/07)
The development of versatile and sustainable catalytic strategies for amide bond formation is a major objective for the pharmaceutical sector and the wider chemical industry. Herein, we report a biocatalytic approach to amide synthesis which exploits the diversity of Nature's amide bond forming enzymes, N-acyltransferases (NATs) and CoA ligases (CLs). By selecting combinations of NATs and CLs with desired substrate profiles, non-natural biocatalytic pathways can be built in a predictable fashion to allow access to structurally diverse secondary and tertiary amides in high yield using stoichiometric ratios of carboxylic acid and amine coupling partners. Transformations can be performed in vitro using isolated enzymes, or in vivo where reactions rely solely on cofactors generated by the cell. The utility of these whole cell systems is showcased through the preparative scale synthesis of a key intermediate of Losmapimod (GW856553X), a selective p38-mitogen activated protein kinase inhibitor.
Comparison of acyl-CoA synthetic activities and enantioselectivity toward 2-arylpropanoic acids in firefly luciferases
Kato, Dai-Ichiro,Yokoyama, Keisuke,Hiraishi, Yoshihiro,Takeo, Masahiro,Negoro, Seiji
experimental part, p. 1758 - 1762 (2012/02/02)
Measurement of thioesterification activities for dodecanoic acid (C12) and ketoprofen was done using five firefly luciferases, from Pyrocoelia miyako (PmL), Photinus pyralis (PpL), Luciola cruciata (LcL), Hotaria parvura (HpL), and Luciola mingrelica (LmL). Among these, PmL, PpL, and LcL showed the expected thioesterification activities toward both substrates. All the enzymes exhibited (R)-enantioselectivity toward ketoprofen, which had same tendency as firefly luciferase from Luciola lateralis (LUC-H). HpL and LmL, however, did not accept ketoprofen, although they had thioesterification activity toward C12. These results indicate that the substrate acceptance of luciferases for the thioesterification reaction varies dramatically relying on the origin of firefly. Hence we focused primarily on PmL and investigated the effect of pH on enzymatic activity. In addition, by determining the kinetic parameters at various pH values, we verified that the kcat parameter contributed to the preferential enantioselectivity of this enzyme.
