| Autor: |
Wiedeman PE; Abbott Laboratories, Pharmaceutical Products Division, 200 Abbott Park Road, Department 47N, Building AP-52N, Abbott Park, Illinois 60064-6217, USA., Fesik SW, Petros AM, Nettesheim DG, Mollison KW, Lane BC, Or YS, Luly JR |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of medicinal chemistry [J Med Chem] 1999 Oct 21; Vol. 42 (21), pp. 4456-61. |
| DOI: |
10.1021/jm980252z |
| Abstrakt: |
C24-Deoxyascomycin was prepared in a two-step process from ascomycin and evaluated for its immunosuppressant activity relative to ascomycin and FK506. An intermediate in the synthetic pathway, Delta(23,24)-dehydroascomycin, was likewise evaluated. Despite lacking the hydrogen-bonding interactions associated with the C24-hydroxyl moiety of ascomycin, C24-deoxyascomycin was found to be equipotent to the parent compound both in its immunosuppressive potency and in its interaction with the immunophilin, FKBP12. Conversely, Delta(23,24)-dehydroascomycin which also lacks the same hydrogen-bonding interactions did not exhibit this potency. NMR studies were conducted on the FKBP12/C24-deoxyascomycin complex in an attempt to understand this phenomenon at the molecular level. The NMR structures of the complexes formed between FKBP12 and ascomcyin or C24-deoxyascomcyin were very similar, suggesting that hydrogen-bonding interactions with the C24 hydroxyl moiety are not important for complex formation. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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