Synthesis and conformational analysis of His-Phe-Arg-Trp-NH2 and analogues with antifungal properties.
The synthesis, in vitro evaluation, and conformational study of His-Phe-Arg-Trp-NH2 and related derivatives acting as antifungal agents are reported. Among them, His-Phe-Arg-Trp-NH2 and His-Tyr-Arg-Trp-NH2 exhibited antifungal activity against Cryptococcus neoformans. Antifungal activity of these compounds appears to be closely related to the alpha-MSH effect. A conformational and electronic study allows us to propose a biologically relevant conformation for these tetrapeptides acting as antifungal agents. In addition, these theoretical calculations permit us to determine the minimal structural requirements to produce the antifungal response and may provide a guide for the design of compounds with this biological activity.
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
Svetaz
Laura
L
Zacchino
Susana A
SA
Somlai
Csaba
C
Csizmadia
Imre G
IG
Penke
Botond
B
Enriz
Ricardo D
RD
D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D003455:Cryptococcus neoformans / Q000187:drug effects; D004583:Electrons; D008958:Models, Molecular; D008968:Molecular Conformation; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D055672:Static Electricity; D013329:Structure-Activity Relationship
D000935:Antifungal Agents; D010455:Peptides