New Peptidomimetics at the Interface: Characterising a Powerful Class of Antimicrobial Molecules

Polymeric biomimetics are important in different biomedical fields including drug delivery and gene transfection as well as many scopes of immunology. While classical polymer synthesis only creates polydisperse polymers with weakly controllable structure and function, the multifunctional peptido- and glycomimetics are monodisperse and perfectly adjustable. That is possible since an increasing toolbox of building blocks is established for the fully automated solid phase peptide synthesizer.

The talk will deal with a novel class of amphiphilic cationic oligoamidoamides also termed β^3R3-peptides as very potent antimicrobial agents and will mainly concentrate on the characterization of their physicochemical parameters.

The techniques used involve amongst others Infrared Reflection-Absorption Spectroscopy (IRRAS) and surface pressure measurements to investigate structural features of amphiphilic cationic β^3R3-peptide sequences at the soft hydrophobic/hydrophilic air/liquid interface. The position of the amide I band in the IRRA spectra was carefully analyzed. Most of the oligomers showed the band at around 1660 cm^-1 characteristic for conformations indicating intramolecular hydrogen bond networks, such as helices. Besides the structural characterization of the pure peptidomimetics, their interaction with different lipid model membranes was also investigated and correlated with the results obtained in biological experiments. The peptides have been injected underneath a pre-compressed lipid monolayer to study the ability of the peptides to penetrate into such layers. All experiments show clearly that this novel class of peptidomimetics combines high and selective antimicrobial activity with exceptionally low cytotoxicity in comparison to values reported in the literature.^[1]

jkeller@mpikg.mpg.de