Chemistry Department Seminar: Tenure Track Candidate
"Bio-inspired materials for drug delivery"
Nature is full of interesting materials, from spider silks that are tougher than Kevlar, mussel adhesives that are effective underwater, and potent venoms that are toxic at low doses. Natural materials, however, require modification for human use. For example, honeybee venom is toxic in part because a small protein component of the venom, a peptide called melittin, will indiscriminately form pores on cell membranes. Therefore redesigning melittin such that it will be triggered to selectively form pores on target membranes could increase their safety and usability. This seminar will focus on how a melittin derivative was modified so that it could act as a portal through which drugs could be delivered to the cytosol of a cell. Drugs that are ingested into a cell are often sequestered in endosomes, which mature into lysosomes. Within lysosomes, the pH drops and the drugs are degraded. To allow drugs to escape from endosomes before they are degraded in lysosomes, we re-designed melittin so it could cause large pores to form only under acidic conditions. We used a high-throughput screen of a combinatorial library of over 18,000 peptides to identify positive hits, which we named the "pHD peptides". They have five or six acidic residues that mediate the pH-triggered pore-formation.
*This seminar counts towards the chemistry major seminar attendance requirement.