Antimicrobial Peptides and Their Superior Fluorinated Analogues: Structure-Activity Relationships as Revealed by NMR Spectroscopy and MD Calculations

作者：Dolores Diaz M; Palomino Schaetzlein Martina; Corzana Francisco; Andreu Cecilia; Carbajo Rodrigo J; del Olmo Marcelli; C****es Mayordomo Angeles; Pineda Lucena Antonio; Asensio Gregorio^*; Jimenez Barbero Jesus

来源：ChemBioChem, 2010, 11(17): 2424-2432.

DOI：10.1002/cbic.201000424

• antimicrobial peptides
• fluorine
• membranes
• molecular dynamics
• NMR spectroscopy
• SDS micelles

The conformations of two synthetic pentapeptides with antimicrobial activity and their 4-fluorophenylalanine (Pff)-containing analogues (ArXArXAr-NH(2); 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 Mn(2+)-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.

• 出版日期2010-11-22