title: Penetratin and derivatives acting as antifungal agents.
abstract: 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.
authors.affiliation: Facultad de Química, Bioquímica y Farmacia, Universidad Nacional de San Luis, Chacabuco 915, 5700 San Luis, Argentina.
authors.forename: Marcelo F
authors.initials: MF
authors.lastname: Masman
authors.forename: Ana M
authors.initials: AM
authors.lastname: Rodríguez
authors.forename: Marcela
authors.initials: M
authors.lastname: Raimondi
authors.forename: Susana A
authors.initials: SA
authors.lastname: Zacchino
authors.forename: Paul G M
authors.initials: PG
authors.lastname: Luiten
authors.forename: Csaba
authors.initials: C
authors.lastname: Somlai
authors.forename: Tamas
authors.initials: T
authors.lastname: Kortvelyesi
authors.forename: Botond
authors.initials: B
authors.lastname: Penke
authors.forename: Ricardo D
authors.initials: RD
authors.lastname: Enriz
mesh_terms: 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
chemical_list: D000935:Antifungal Agents; D002352:Carrier Proteins; D057846:Cell-Penetrating Peptides; D009842:Oligopeptides; C414409:penetratin