Penetratin and derivatives acting as antifungal agents.
The synthesis, in vitro evaluation, and conformational study of RQIKIWFQNRRMKWKK-NH(2) (penetratin) and related derivatives acting as antifungal agents are reported. Penetratin and some of its derivatives displayed antifungal activity against the human opportunistic pathogenic standardized ATCC strains Candida albicans and Cryptococcus neoformans as well as clinical isolates of C. neoformans. Among the compounds tested, penetratin along with the nonapeptide RKWRRKWKK-NH(2) and the tetrapeptide RQKK-NH(2) exhibited significant antifungal activities against the Cryptococcus species. A comprehensive conformational analysis on the peptides reported here using three different approaches, molecular mechanics, simulated annealing and molecular dynamics simulations, was carried out. The experimental and theoretical results allow us to identify a topographical template which may provide a guide for the design of new compounds with antifungal characteristics against C. neoformans.
Masman
Marcelo F
MF
Facultad de Química, Bioquímica y Farmacia, Universidad Nacional de San Luis, Chacabuco 915, 5700 San Luis, Argentina.
Rodríguez
Ana M
AM
Raimondi
Marcela
M
Zacchino
Susana A
SA
Luiten
Paul G M
PG
Somlai
Csaba
C
Kortvelyesi
Tamas
T
Penke
Botond
B
Enriz
Ricardo D
RD
D000595:Amino Acid Sequence; D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002176:Candida albicans / Q000187:drug effects; D002352:Carrier Proteins / Q000138:chemical synthesis* / Q000494:pharmacology; D057846:Cell-Penetrating Peptides; D003455:Cryptococcus neoformans / Q000187:drug effects; D006801:Humans; D008968:Molecular Conformation; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000935:Antifungal Agents; D002352:Carrier Proteins; D057846:Cell-Penetrating Peptides; D009842:Oligopeptides; C414409:penetratin