Total synthesis and antifungal evaluation of cyclic aminohexapeptides |
| |
Authors: | Klein L L Li L Chen H J Curty C B DeGoey D A Grampovnik D J Leone C L Thomas S A Yeung C M Funk K W Kishore V Lundell E O Wodka D Meulbroek J A Alder J D Nilius A M Lartey P A Plattner J J |
| |
Affiliation: | Infectious Disease Research, Abbott Laboratories, Abbott Park, IL 60064-3500, USA. larry.l.klein@abbott.com |
| |
Abstract: | 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. |
| |
Keywords: | |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|