title: Penetratin analogues acting as antifungal agents.
abstract: The synthesis, in vitro evaluation, and conformational study of penetratin analogues acting as antifungal agents are reported. Different peptides structurally related with penetratin were evaluated. Analogues of penetratin rich in Arg, Lys and Trp amino acids were tested. In addition, HFRWRQIKIWFQNRRM[O]KWKK-NH(2), a synthetic 20 amino acid peptide was also evaluated. These penetratin analogues displayed antifungal activity against human pathogenic strains including Candida albicans and Cryptococcus neoformans. In contrast, Tat peptide, a well-known cell penetrating peptide, did not show a significant antifungal activity against fungus tested here. We also performed a conformational study by means experimental and theoretical approaches (CD spectroscopic measurements and MD simulations). The electronic structure analysis was carried out from Molecular Electrostatic Potentials (MEP) obtained by using RHF/6-31G ab initio calculations. Our experimental and theoretical results permitted us to identify a topographical template which may provide a guide for the design of new peptides with antifungal effects.
authors.affiliation: Facultad de Química, Bioquímica y Farmacia, Universidad Nacional de San Luis, Chacabuco 915, 5700 San Luis, Argentina.
authors.forename: Francisco M
authors.initials: FM
authors.lastname: Garibotto
authors.forename: Adriana D
authors.initials: AD
authors.lastname: Garro
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: Andras
authors.initials: A
authors.lastname: Perczel
authors.forename: Csaba
authors.initials: C
authors.lastname: Somlai
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 / Q000737:chemistry* / Q000494:pharmacology*; D002352:Carrier Proteins / Q000737:chemistry* / Q000494:pharmacology*; D057846:Cell-Penetrating Peptides; D002942:Circular Dichroism; D005658:Fungi / Q000187:drug effects*; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D009010:Monte Carlo Method; D011487:Protein Conformation; D055672:Static Electricity
chemical_list: D000935:Antifungal Agents; D002352:Carrier Proteins; D057846:Cell-Penetrating Peptides; C414409:penetratin