AI Article Synopsis
- C24-Deoxyascomycin was synthesized from ascomycin and tested for immunosuppressant activity, showing comparable potency to ascomycin and FK506 despite lacking certain hydrogen-bonding features.
- The intermediate compound, Delta(23,24)-dehydroascomycin, did not demonstrate similar immunosuppressive effects, indicating that those features are crucial for activity.
- NMR studies revealed that the structures of FKBP12 complexes with ascomycin and C24-deoxyascomycin are very similar, suggesting that the C24 hydroxyl group's hydrogen-bonding is not essential for the complex's formation.
Article Abstract
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.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1021/jm980252z | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!