| From Antimicrobials to Cell Penetrating Peptides: Molecular 'Hole Punchers' and Their Mechanisms |
| Abstract ID | LCLS/SSRL-17 |
| Presenter | Gerard
Wong |
| Presentation Type | LCLS/SSRL Invited Speaker
|
| Full Author List | Gerard C. L. Wong (1)
|
| Affiliations | (1) University of Illinois, Dept. of Materials Science and Engineering, Dept. of Physics, Dept. of Bioengineering
|
| Category | Bio/Life Sciences |
| Abstract | Antimicrobial peptides comprise a key component of innate immunity for a wide range of multicellular organisms. It has been shown that natural antimicrobial peptides and their analogs can permeate bacterial membranes but not host membranes. There are a number of proposed models for this action, but the detailed molecular mechanism of the induced membrane permeation remains unclear. We systematically investigate interactions and self-assembled structures formed by model bacterial membranes and a prototypical family of small molecule antimicrobials with controllable activity and selectivity. Synchrotron small angle x-ray scattering results correlate antibacterial activity and the induced formation of an inverted hexagonal phase, and indicate that the organization of negative curvature lipids such as DOPE are crucially important. Plate killing assays of DOPE-deficient mutant bacteria agree with the x-ray results. The general principles governing the action of membrane active antimicrobials are cognate to cell penetrating peptides such as TAT from the HIV virus and ANTP from the fruit fly. Homologies as well as differences between these systems will be compared. |
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| Funding Acknowledgement | |
