Antihistoplasmal in vitro and in vivo effect of Lys-Nva-FMDP.
The new synthetic antifungal agent, L-Lysyl-L-Norvalyl-FMDP, inhibits growth of the yeast form of Histoplasma capsulatum. The compound is transported into the fungal cells by peptide permeases, cleaved intracellularly to constitutive amino acids, and the released C-terminal amino acid inhibits glucosamine-6-phosphate synthase. Promising antihistoplasmal in vivo activity of the FMDP-peptide was observed in an organ load test in mice.
Milewski
S
S
Department of Pharmaceutical Technology and Biochemistry, Technical University of Gdańsk, Poland.milewski@altis.chem.pg.gda.pl
Mignini
F
F
Micossi
L
L
Borowski
E
E
D000818:Animals; D000935:Antifungal Agents / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D001692:Biological Transport; D005260:Female; D005945:Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing) / Q000037:antagonists & inhibitors; D006658:Histoplasma / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D006660:Histoplasmosis / Q000188:drug therapy* / Q000473:pathology; D007700:Kinetics; D026901:Membrane Transport Proteins / Q000378:metabolism; D051379:Mice; D013154:Spleen / Q000382:microbiology / Q000473:pathology; D015091:beta-Alanine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use
D000935:Antifungal Agents; C116677:Lys-Nva-FMDP; D026901:Membrane Transport Proteins; D015091:beta-Alanine; C043912:peptide permease; D005945:Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing)