Abstract
Abstract Polyoxins and nikkomycins are a class of naturally occurring peptidyl nucleoside antibiotics that show promise as potential antifungal agents due to their potent ability to inhibit chitin synthase, an enzyme responsible for fungal cell wall biosynthesis. Whole cell assays and in vivo studies have shown that these natural products have poor cellular uptake and are metabolically unstable, and there has been a concerted effort to improve their pharmokinetic properties by synthesizing analogs. These have either been designed as natural substrate analogs, transition state mimetics or mechanistic inhibitors. Recent synthetic efforts and the results of their biological studies are briefly described in this review, and the current trends in the design and construction of polyoxin and nikkomycin analogs are discussed.
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