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Antifungal dipeptides incorporating an inhibitor of homoserine dehydrogenase
Author(s) -
Skwarecki Andrzej S.,
Schielmann Marta,
Martynow Dorota,
Kawczyński Marcin,
Wiśniewska Aleksandra,
Milewska Maria J.,
Milewski Sławomir
Publication year - 2018
Publication title -
journal of peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 66
eISSN - 1099-1387
pISSN - 1075-2617
DOI - 10.1002/psc.3060
Subject(s) - dipeptide , efflux , biochemistry , chemistry , intracellular , cytosol , oligopeptide , amino acid , homoserine , norvaline , mechanism of action , enzyme , peptide , in vitro , gene , virulence , quorum sensing , leucine
The antifungal activity of 5‐hydroxy‐4‐oxo‐ l ‐norvaline (HONV), exhibited under conditions mimicking human serum, may be improved upon incorporation of this amino acid into a dipeptide structure. Several HONV‐containing dipeptides inhibited growth of human pathogenic yeasts of the Candida genus in the RPMI‐1640 medium, with minimal inhibitory concentration values in the 32 to 64 μg mL −1 range. This activity was not affected by multidrug resistance that is caused by overexpression of genes encoding drug efflux proteins. The mechanism of antifungal action of HONV dipeptides involved uptake by the oligopeptide transport system, subsequent intracellular cleavage by cytosolic peptidases, and inhibition of homoserine dehydrogenase by the released HONV. The relative transport rates determined the anticandidal activity of HONV dipeptides.