Antimicrobial Peptides and Their Superior Fluorinated Analogues: Structure-Activity Relationships as Revealed by NMR Spectroscopy and MD Calculations
Por:
M. DIAZ, M. PALOMINO-SCHATZLEIN, F. CORZANA, C. ANDREU, R. CARBAJO, M. DEL OLMO, A. CANALES-MAYORDOMO, A. PINEDA-LUCENA, G. ASENSIO and J. JIMENEZ-BARBERO
Publicada:
22 nov 2010
Resumen:
The conformations of two synthetic pentapeptides with antimicrobial activity and their 4-fluorophenylalanine (Pff)-containing analogues (ArXArXAr-NH2; Ar=Phe, Pff; X=Lys, Arg) have been studied. NMR experiments carried out both in aqueous fluoroalcohol solutions and SDS micelles permitted their interactions with membrane-like environments to be explored. WaterLOGSY experiments and Mn2+-based paramagnetic probes were also applied to assess their orientations with respect to the SDS micelles. In addition, pulse-field gradient (PFG) diffusion NMR spectroscopy studies were conducted, under different experimental conditions (i.e., concentration, temperature) to characterize the possible changes in the peptides' aggregation states as a putative critical factor for their antimicrobial activity. Finally, molecular dynamics simulations on a variety of conformations showed the intrinsic flexibility of these peptides in both aqueous solutions and membrane-mimetic systems.
Filiaciones:
M. DIAZ:
CSIC, Ctr Invest Biol, Dept Biol Fis Quim, Madrid 28040, Spain
:
Ctr Invest Principe Felipe, Dept Quim Med, Lab Bioquim Estruct, Valencia 46012, Spain
F. CORZANA:
Univ La Rioja, UA CSIC, Dept Quim Organ, Logrono 26006, Spain
C. ANDREU:
Univ Valencia, Fac Farm, Dept Quim Organ, E-46010 Valencia, Spain
:
Ctr Invest Principe Felipe, Dept Quim Med, Lab Bioquim Estruct, Valencia 46012, Spain
M. DEL OLMO:
Univ Valencia, Dept Bioquim & Biol Mol, E-46100 Valencia, Spain
A. CANALES-MAYORDOMO:
Univ Complutense Madrid, Fac Quim, Dept Quim Organ 1, E-28040 Madrid, Spain
:
Ctr Invest Principe Felipe, Dept Quim Med, Lab Bioquim Estruct, Valencia 46012, Spain
G. ASENSIO:
Univ Valencia, Fac Farm, Dept Quim Organ, E-46010 Valencia, Spain
J. JIMENEZ-BARBERO:
CSIC, Ctr Invest Biol, Dept Biol Fis Quim, Madrid 28040, Spain
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