SpeakerProf. Ashutosh Chilkoti, Duke, Biomedical Engineering, Host: Dan Morse & Jacob Israelachvili
Date and LocationWednesday September 28, 2016 11:00am to 12:00pm
Recombinant Peptide Polymers that Display Aqueous Phase behavior: From Sequence to Applications
Elastin like polypeptides (ELPs) are the best studied class of peptide polymers that exhibit lower critical solution temperature (LCST) phase behavior in water, and these polymers have enabled innovative approaches to nanoparticle self-assembly, cancer therapy, regenerative medicine and protein purification.
In the first part of my talk, I will discuss a general method, attachment-triggered self-assembly of recombinant peptide polymers that packages small hydrophobic molecules into soluble polymer nanoparticles. Because many cancer chemotherapeutics are insoluble small molecules with poor bioavailability, this approach has great utility to increase the solubility, plasma half-life and tumor accumulation of many cancer chemotherapeutics.
In the second part of my talk I will focus on how little was known, till recently, about how LCST phase behavior is encoded in peptide polymers at their amino acid —primary— sequence level. To understand the sequence determinants of LCST phase behavior, I will present data that uses bioinformatics to guide the synthesis of a large family of peptide polymers that are predicted to exhibit LCST phase behavior. Analysis of the LCST phase behavior of these polymers provides sequence heuristics to encode LCST phase behavior in intrinsically disordered peptide polymers and enables the design of polymers that encode two orthogonal functions —phase behavior and bioactivity— seamlessly at the primary sequence level. These studies also identified polymers that display tunable degrees of thermal hysteresis in their LCST phase behavior, a property that is exploited for the design of thermal “shape memory” nanoparticles.