Developing Membrane Active Peptides for Endosomal Escape of Macromolecules
Wiedman, Gregory R.
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Membrane Active Peptides (MAPs) are an important class of short protein sequences that hold the potential to be used for a number of varied purposes such as antibacterial, antiviral, and drug delivery based therapies. Despite this great potential, the development of MAPs has been hindered by a lack of consensus about their mechanisms of activity. Herein we proposed that MAPs can be categorized into several categories differentiating how they interact with model cell membranes. In this dissertation we examined how these activities can be regulated by pH. We used this information to design and test MAPs with pH-dependant activity for drug delivery through both rational design and high-throughput screening. Finally, we tested our peptides both with model biophysical characterization techniques as well as cell based assays and made connections between the two. Our intention is that the work conducted in this dissertation will provide a framework for the development of effective and efficient Membrane Active Peptides.