RESUMO
S-Adenosylmethionine (SAM) synthase was engineered for biocatalytic production of SAM and long-chain analogues by rational re-design. Substitution of two conserved isoleucine residues extended the substrate spectrum of the enzyme to artificial S-alkylhomocysteines. The variants proved to be beneficial in preparative synthesis of SAM (and analogues) due to a much reduced product inhibition.
Assuntos
Homocisteína/biossíntese , Metionina Adenosiltransferase/antagonistas & inibidores , Metionina Adenosiltransferase/metabolismo , Engenharia de Proteínas , Bacillus subtilis/enzimologia , Variação Genética/genética , Homocisteína/análogos & derivados , Homocisteína/química , Metionina Adenosiltransferase/genética , Estrutura MolecularRESUMO
HPLC-UV and MS/MS studies of impurity profiles of original (Xenical, F. Hoffmann-La Roche Ltd., Switzerland) and generic (Cobese, Ranbaxy Laboratories Limited, India, and Orsoten, KRKA, Russia) products were carried out. The drug and related impurities were extracted by dissolving commercial samples in ethanol. The generic formulations contained higher levels of impurities than the original product. Impurity profiles (HPLC-MS/MS) of the generic samples are similar among themselves, whilst different in comparison to the impurity profile of the original product. The number of detected impurities for generics (14 impurities in Cobese and 13 impurities in Orsoten) is higher than for the original product (3 impurities in Xenical). Based on these analyses the overall analytical quality follows the order Xenical (best)>Orsoten>Cobese.
Assuntos
Fármacos Antiobesidade/análise , Cromatografia Líquida de Alta Pressão/métodos , Contaminação de Medicamentos , Lactonas/análise , Espectrometria de Massas em Tandem/métodos , OrlistateRESUMO
2,4-Dimethoxy-2-methyl-6H-pyran-3-one (1), a hitherto unknown natural product, and the calcium salt of rehmapicroside (2) have been isolated from rhizomes of the Vietnamese variety of Rehmannia glutinosa Libosch together with a series of known compounds: norcarotenoids (3-5), 2-formyl-5-hydroxy-methylfurane (6), the iridoid rehmaglutin D (7), iridoid glycosides (8-12) and phenylethyl alcohol glycosides (13-17). Their structures were determined by mass and NMR spectroscopy.
Assuntos
Pironas/química , Rehmannia/química , Sequência de Carboidratos , Espectroscopia de Ressonância Magnética , Dados de Sequência Molecular , Extratos Vegetais/química , Raízes de Plantas/química , Espectrometria de Massas por Ionização por ElectrosprayRESUMO
Natural products cover a diversity space not yet available from synthetic libraries, with an unrivalled success rate as drug leads. The combinatorial synthesis of non-oligomeric natural-product-based libraries, however, is still limited to few examples because access to easily modified units strongly depends on the availability of a core structure either from a natural source, or through a suitable synthetic route. Only a few resourceful groups have managed the latter approach for more demanding multifunctional natural drug leads, such as epothilones.
