title: Structure-activity relationships of the nikkomycins.
abstract: The structure-activity relationships of different nikkomycins were studied to evaluate the structural requirements for a potent chitin synthase inhibitor. We investigated the transport of the nikkomycins via the peptide transport system of the yeast Yarrowia lipolytica and determined the kinetic parameters for nikkomycin Z uptake [Km = 24 microM, Vmax = 2.2 nmol min-1 (mg dry wt)-1]. We demonstrated that the beta-methyl group of the N-terminal amino acid of dipeptide nikkomycins protects the molecule against peptidase activity in crude cell-extracts of different fungi. Furthermore, the relationship between inhibition constants for chitin synthase, transport of the nikkomycins via the peptide transport system, susceptibility to degradation by cellular proteases and whole-cell activity of the nikkomycins are discussed.
authors.affiliation: Universität Tübingen, Biologisches Institut, Tübingen, FRG.
authors.forename: H
authors.initials: H
authors.lastname: Decker
authors.forename: H
authors.initials: H
authors.lastname: Zähner
authors.forename: H
authors.initials: H
authors.lastname: Heitsch
authors.forename: W A
authors.initials: WA
authors.lastname: König
authors.forename: H P
authors.initials: HP
authors.lastname: Fiedler
mesh_terms: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D000935:Antifungal Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D001693:Biological Transport, Active / Q000502:physiology; D002687:Chitin Synthase / Q000037:antagonists & inhibitors*; D002851:Chromatography, High Pressure Liquid; D003302:Coprinus / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D010450:Endopeptidases / Q000378:metabolism; D007700:Kinetics; D011487:Protein Conformation; D004718:Saccharomycetales / Q000187:drug effects / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; C011952:nikkomycin; D002687:Chitin Synthase; D010450:Endopeptidases