Open AccessA comparison of the chitin synthase‐inhibitory and antifungal efficacy of nucleoside‐peptide antibiotics: structure‐activity relationships
Author(s) -
Furter Rolf,
Rast Dora M.
Publication year - 1985
Publication title -
fems microbiology letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.899
H-Index - 151
eISSN - 1574-6968
pISSN - 0378-1097
DOI - 10.1111/j.1574-6968.1985.tb00792.x
Subject(s) - tripeptide , antagonism , nucleoside , chitin synthase , dipeptide , chitin , peptide , biology , biochemistry , stereochemistry , minimum inhibitory concentration , in vivo , lipopeptide , biological activity , antibiotics , chemistry , in vitro , receptor , bacteria , chitosan , genetics , microbiology and biotechnology
Using Mucor rouxii , the chitin synthase (ChS)‐inhibitory and antifungal activity was determined of 6 nucleoside‐peptide antibiotics (NPAs) representing pairs of structural analogues, each consisting of a dipeptide (DP) and a corresponding tripeptide (TP). These were the nikkomycins X and I (X, I), the nikkomycins Z and J (Z, J), and the polyoxins D and A (D, A). Although all were very good ChS‐inhibitors (X and A being best, with K i approx. 0.5 μM), only X and Z elicited a strong response in vivo as determined by the degree of inhibition exerted on N ‐acetylglucosamine (GlcNAc) incorporation into the chitin fraction, the survival rate, and the minimum inhibitory concentration (MIC). The MIC values were about 2 μM (for X and Z) and 100 μM (for I, J, D and A). Certain DPs and TPs reduced the antifungal activity of X, the effect being much more pronounced with DPs. It is suggested that uptake of NPAs involves the transpeptidase reaction of the γ‐glutamyl cycle, the observed antagonism thus resulting from competition for a common carrier.