Recent Developments in Elastin-like Polypeptides: New Motifs and New Self-Assembling Systems

Ashutosh Chilkoti
Duke University
Thursday, March 29, 2012
NCCU 2050 Brite | 4:00pm

This talk will describe new developments in my laboratory in the design, synthesis, self-assembly and application of stimulus responsive peptide polymers. In the first half of my talk, I will describe the rich capacity of elastin-like polypeptides (ELPs) –a class of recombinant peptide polymers of a Val-Pro-Gly-Xaa-Gly (VPGXG) repeat unit that display lower critical solution temperature transition (LCST) phase behavior in aqueous solution– to self-assemble into nanostructures in response to a range of stimuli. In one example of this behavior, we designed a chimeric polypeptide that consists of two segments: (VPGXG)n repeats followed by a short (GGY)n segment, and showed that attachment of multiple copies of a hydrophobic molecule at the Y position can impart sufficient amphiphilicity to the polypeptide and thereby drive its self-assembly into near-monodisperse nanoparticles with the attached hydrophobic small molecule embedded in the core of the nanoparticle. Because many cancer chemotherapeutics are insoluble hydrophobic small molecules with poor bioavailability, this approach of attachment-triggered encapsulation of small hydrophobic molecules into soluble nanoparticles has great utility to increase the solubility, plasma half-life and tumor accumulation of cancer chemotherapeutics. In another example, I will discuss triple-responsive diblock ELPs that self-assemble into monodisperse micelles in response to a thermal trigger, that can be further stabilized by metal ion chelation within the core of the micelle and that disassemble in response to a small drop in pH.  In the second half of my talk, I will describe recent work wherein we have identified a large number of peptide polymers –syntactomers– that display LCST phase behavior, with a syntax that ranges from a collection of simple peptide repeats (“words”) reminiscent of synthetic polymers composed of macromonomers to syntactomers that approach the sequence complexity of proteins (“phrases”), and illustrate that syntax may be a useful concept in the design of peptide based polymers. Recombinant peptide polymers provide rich opportunities for application in biotechnology and medicine, and a few applications of these biomacromolecules will also be highlighted in this talk.