PEPTIDE INTERACTION MECHANISM WITH LAMELLAR LIPID BILAYERS: VARIANTS OF C3A PEPT

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Mounting problems of multidrug resistance in bacterial infections has produced a need for new types of antibiotics. This need has in turn prompted an augmented interest in antimicrobial peptides (AMP). It has been found that such peptides are fast in their action, and current data also indicate that bacteria only develop limited resistance against antimicrobial peptides. One problem with such peptides, however, is the issue of selectivity. The peptides are efficient against bacteria but also harmful to human cells. Much work has been devoted to this issue, using approaches such as screening libraries and peptides identified from other species. Our proposal aims to investigate how the action of antimicrobial peptides can be coupled with structural descriptors, such as net charge, hydrophobicity, and secondary structure patterns to improve efficacy. Our focus will be generating new knowledge regarding the incorporation alternative mechanism of C3a-derived peptide CNY21 and its variants CNY21L and CNY21K into lamellar lipid bilayers. The mechanism for CNY21 and its variants is, at the moment, unclear. Possibilities include anything from packing defects to pore formation, and may even be as simple as membrane thinning. For this project we propose to use a combination of small angle x-ray diffraction (SAXD) and grazing incidence small-angle x-ray scattering (GISAXS) on highly aligned multi-lamellar peptide membrane systems to elucidate the structural basis of the membrane activity of these new antimicrobial peptides.