| Revue: | Anais da Academia Brasileira de Ciencias |
| Base de datos: | PERIÓDICA |
| Número de sistema: | 000412236 |
| ISSN: | 0001-3765 |
| Autores: | Oliveira, Simone S.S1 Bello, Murilo L2 Rodrigues, Carlos R2 Azevedo, Paula L3 Ramos, Maria C.K.V3 Aquino-Neto, Francisco R. de3 Fiaus, Sorele B1 Dias, Luiza R.S1 |
| Instituciones: | 1Universidade Federal Fluminense, Faculdade de Farmacia, Niteroi, Rio de Janeiro. Brasil 2Universidade Federal do Rio de Janeiro, Faculdade de Farmacia, Rio de Janeiro. Brasil 3Universidade Federal do Rio de Janeiro, Instituto de Quimica, Rio de Janeiro. Brasil |
| Año: | 2017 |
| Periodo: | Sep |
| Volumen: | 89 |
| Número: | 3 |
| Paginación: | 1403-1416 |
| País: | Brasil |
| Idioma: | Inglés |
| Tipo de documento: | Artículo |
| Enfoque: | Experimental, aplicado |
| Resumen en inglés | This study presents the bioreduction of six β-ketoesters by whole cells of Kluyveromyces marxianus and molecular investigation of a series of 13 β-ketoesters by hologram quantitative structure-activity relationship (HQSAR) in order to relate with conversion and enantiomeric excess of β-stereogenic-hydroxyesters obtained by the same methodology. Four of these were obtained as (R)-configuration and two (S)-configuration, among them four compounds exhibited >99% enantiomeric excess. The β-ketoesters series LUMO maps showed that the β-carbon of the ketoester scaffold are exposed to undergo nucleophilic attack, suggesting a more favorable β-carbon side to enzymatic reduction based on adopted molecular conformation at the reaction moment. The HQSAR method was performed on the β-ketoesters derivatives separating them into those provided predominantly (R)- or (S)-β-hydroxyesters. The HQSAR models for both (R)- and (S)-configuration showed high predictive capacity. The HQSAR contribution maps suggest the importance of β-ketoesters scaffold as well as the substituents attached therein to asymmetric reduction, showing a possible influence of the ester group carbonyl position on the molecular conformation in the enzyme catalytic site, exposing a β-carbon side to the bioconversion to (S)- and (R)-enantiomers |
| Disciplinas: | Química |
| Palabras clave: | Química farmacéutica, Biotecnología, Beta-cetoésteres, Beta-hidroxiésteres, Biocatálisis, Kluyveromyces marxianus, Biorreducción, Enantiómeros |
| Keyword: | Chemistry, Medicinal chemistry, Biotechnology, Beta-ketoesters, Beta-hydroxyesters, Biocatalysis, Kluyveromyces marxianus, Bioreduction, Enantiomers |
| Texte intégral: | Texto completo (Ver HTML) |
