Total synthesis and antifungal evaluation of cyclic aminohexapeptides
| Autor: | Leping Li, Paul A. Lartey, J. J. Plattner, Cynthia B. Curty, Clinton M. Yeung, Christina Louise Leone, Jeffrey Alder, Sheela A. Thomas, Hui-Ju Chen, Angela M. Nilius, Edwin O. Lundell, J. Meulbroek, David A. Degoey, Dariusz Wodka, Kenneth W. Funk, Vimal Kishore, David J. Grampovnik, Larry L. Klein |
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| Rok vydání: | 2000 |
| Předmět: |
Antifungal Agents
Proline Stereochemistry Clinical Biochemistry Pharmaceutical Science Microbial Sensitivity Tests Peptides Cyclic Biochemistry Chemical synthesis Fungal Proteins Echinocandins Mice Structure-Activity Relationship chemistry.chemical_compound Echinocandin B Amphotericin B Yeasts Drug Discovery Animals Structure–activity relationship Amines Molecular Biology Candidiasis Vulvovaginal Candida Glucan chemistry.chemical_classification Fungal protein Dose-Response Relationship Drug Chemistry Organic Chemistry Total synthesis Cyclic peptide Anti-Bacterial Agents Disease Models Animal Solubility Acute Disease Molecular Medicine Female Peptides |
| Zdroj: | Bioorganic & Medicinal Chemistry. 8:1677-1696 |
| ISSN: | 0968-0896 |
| DOI: | 10.1016/s0968-0896(00)00097-3 |
| Popis: | The need for new therapies to treat systemic fungal infections continues to rise. Naturally occurring hexapeptide echinocandin B (1) has shown potent antifungal activity via its inhibition of the synthesis of beta-1,3 glucan, a key fungal cell wall component. Although this series of agents has been limited thus far based on their physicochemical characteristics, we have found that the synthesis of analogues bearing an aminoproline residue in the 'northwest' position imparts greatly improved water solubility (> 5 mg/mL). The synthesis and structure-activity relationships (SAR) based on whole cell and upon in vivo activity of the series of compounds are reported. |
| Databáze: | OpenAIRE |
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