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The pH-Low Insertion Peptide (pHLIP): From Understanding Mechanism to Applications

This is a past event.

Friday, November 1, 2019 at 11:00am to 12:00pm

MMC polycom to BBC, AHC3 205 (MMC) and AC2 210 (BBC)

Join us for a talk on " The pH-Low Insertion Peptide (pHLIP): From Understanding Mechanism to Applications" with Dr. Ming An, Associate Professor, SUNY-Binghamton University, Department of Chemistry.

The pH-low insertion peptide (pHLIP) inserts into membrane under mild acidity, forming a transmembrane α-helix. For applications, pHLIP can (a) detect local acidosis in vivo (e.g. for cancer imaging), and (b) translocate polar, otherwise membrane-impermeable cargos across membrane, which has far-reaching implications in research and medicine. With its origin as the transmembrane (TM) helix C of bacteriorhodopsin, pHLIP is also an important model for understanding how pH can affect the folding and topogenesis of a TM α-helix. Although the initial and end states of pHLIP insertion (at pH greater than or equal to 7 and less than or equal to 5.3, respectively) are well known, how pHLIP interacts with membrane at the intervening pH values, which are most relevant to tumor acidity in vivo, are not clear. In the past few years, in collaboration with the Wei Qiang group, we used solid-state NMR to establish the distinct intermediate states that exist at the intervening pH values. Efforts in using this information to design variants with im-proved properties (e.g. insertion at higher pH) will be discussed. Other topics include (a) pHLIP – cell interactions and (b) using pHLIP as a model TM helix for developing new cross-linking chemistry between membrane protein and lipids.