2078-13-9Relevant articles and documents
Synthesis of N-[4-(2'-[18F]fluoroalkoxybenzoyl)]- And N-(3-[123I]iodo-4-methoxybenzoyl)pyrrolidin-2-ones as potential brain imaging agents
Akula, Murthy,Blevins, David,Kabalka, George W.,Osborne, Dustin
, p. 1226 - 1236 (2019/07/31)
– The microfluidic synthesis of promising brain imaging PET agents N-[4-(2’-[18F]fluoroalkyloxybenzoyl)]pyrrolidin-2-ones 13a-c was accomplished by nucleophilic radiofluorination of the corresponding tosylate precursors 9a-c with Kryptofix-pota
Investigation of the substrate range of CYP199A4: Modification of the partition between hydroxylation and desaturation activities by substrate and protein engineering
Bell, Stephen G.,Zhou, Ruimin,Yang, Wen,Tan, Adrian B. H.,Gentleman, Alexander S.,Wong, Luet-Lok,Zhou, Weihong
, p. 16677 - 16688 (2013/03/28)
The cytochrome P450 enzyme CYP199A4, from Rhodopseudomonas palustris HaA2, can efficiently demethylate 4-methoxybenzoic acid. It is also capable of oxidising a range of other related substrates. By investigating substrates with different substituents and ring systems we have been able to show that the carboxylate group and the nature of the ring system and the substituent are all important for optimal substrate binding and activity. The structures of the veratric acid, 2-naphthoic acid and indole-6-carboxylic acid substrate-bound CYP199A4 complexes reveal the substrate binding modes and the side-chain conformational changes of the active site residues to accommodate these larger substrates. They also provide a rationale for the selectivity of product oxidation. The oxidation of alkyl substituted benzoic acids by CYP199A4 is more complex, with desaturation reactions competing with hydroxylation activity. The structure of 4-ethylbenzoic acid-bound CYP199A4 revealed that the substrate is held in a similar position to 4-methoxybenzoic acid, and that the C β C-H bonds of the ethyl group are closer to the heme iron than those of the Cα (3.5 vs. 4.8 A?). This observation, when coupled to the relative energies of the reaction intermediates, indicates that the positioning of the alkyl group relative to the heme iron may be critical in determining the amount of desaturation that is observed. By mutating a single residue in the active site of CYP199A4 (Phe185) we were able to convert the enzyme into a 4-ethylbenzoic acid desaturase. Engineering a P450 desaturase: The substrate range of CYP199A4 from Rhodopseudomonas palustris was investigated. The partition between the hydroxylation and desaturation activities of 4-ethylbenzoic acid was studied by changing the substrate and by mutation. The activity of CYP199A4 with 4-ethylbenzoic acid was changed to a desaturase by a single mutation at F185. Copyright
Characterization of phenolic compounds in rooibos tea
Krafczyk, Nicole,Glomb, Marcus A.
, p. 3368 - 3376 (2008/09/20)
Polyphenols present in rooibos, a popular herbal tea from Aspalathus linearis, were isolated in two steps. First, phenolic ingredients were separated by multilayer countercurrent chromatography (MLCCC). Preparative high-performance liquid chromatography (HPLC) was then applied to obtain pure flavonoids. The purity and identity of isolated compounds was confirmed by different NMR experiments, HPLC-diode array detector (DAD), or gas chromatography-mass spectrometry (GC-MS) analysis. This strategy proved to be valid to isolate material in up to gram quantities and to verify known and previously not published polyphenol structures. In addition the chemistry of dihydrochalcones and related intermediates was studied. The dihydrochalcone aspalathin was oxidized to the corresponding flavanone-C-glycosides ((R)/(S)-eriodictyol-6-C-β-D-glucopyranoside and (R)/(S)-eriodictyol-8-C- β-D-glucopyranoside). Flavanone-6-C-β-D-glucopyranosides were further degraded to flavones isoorientin and orientin.
