Synthesis of new polyoxin derivatives and their activity against chitin synthase from Candida albicans.
Two analogues of L-alanylpolyoxin C with a modified peptide bond were synthesized and tested for inhibition of chitin synthase in Candida albicans. N-Methylation of the peptide bond (compound 13) or the replacement of it by NH2CH2 (compound 9) led to loss of activity in the enzyme assay. A novel analogue (compound 5) of nikkomycin was synthesized from uracil polyoxin C and (2S,3R)-3-hydroxyhomotyrosine, a component of echinocandin C. Despite high activity in the chitin synthase assay, 5 had no inhibitory effect on cells of C. albicans.
Emmer
G
G
Ryder
N S
NS
Grassberger
M A
MA
D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002176:Candida albicans / Q000201:enzymology*; D002687:Chitin Synthase / Q000037:antagonists & inhibitors*; D005964:Glucosyltransferases / Q000037:antagonists & inhibitors*; D010455:Peptides / Q000138:chemical synthesis / Q000494:pharmacology; D011741:Pyrimidine Nucleosides / Q000138:chemical synthesis / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000935:Antifungal Agents; D010455:Peptides; D011741:Pyrimidine Nucleosides; C002457:polyoxin; D005964:Glucosyltransferases; D002687:Chitin Synthase