New small-size peptides possessing antifungal activity

FRANCISCO M. GARIBOTTO; ADRIANA D. GARRO; MARCELO F. MASMAN; ANA M. RODRÍGUEZ; PAUL G. M. LUITEN; MARCELA RAIMONDI; SUSANA A. ZACCHINO; CSABA SOMLAI; BOTOND PENKE; RICARDO D. ENRIZ

BIOORGANIC & MEDICINAL CHEMISTRY.

PERGAMON-ELSEVIER SCIENCE LTD

Año: 2010 vol. 18 p. 158 - 167

0968-0896

The synthesis, in vitro evaluation, and conformational study of a new series of small-size peptides acting as antifungal agents are reported. In a first step of our study we performed a conformational analysis using Molecular Mechanics calculations. The electronic study was carried out using Molecular electrostatic potentials (MEPs) obtained from RHF/6-31G calculations. On the basis of the theoretical predictions three small-size peptides, RQWKKWWQWRR-NH2, RQIRRWWQWRR-NH2, and RQIRRWWQW-NH2 were synthesized and tested. These peptides displayed a significant antifungal activity against human pathogenic strains including Candida albicans and Cryptococcus neoformans. Our experimental and theoretical results allow the identification of a topographical template which can serve as a guide for the design of new compounds with antifungal properties for potential therapeutic applications against these pathogenic fungi.