School Seminar: Professor Nathan Gianneschi; Northwestern University – School of Chemistry School Seminar: Professor Nathan Gianneschi; Northwestern University – School of Chemistry

School Seminar: Professor Nathan Gianneschi; Northwestern University

Friday, 27 August 11:00am – 12:00pm

This seminar will be delivered via Zoom – Please email chemistry.researchsupport@sydney.edu.au for zoom link and password.

Speaker: Professor Nathan Gianneschi; Northwestern University

Host: Professor Louis Rendina

 

Title: Protein-Like Polymers as Proteomimetic Therapeutics

Abstract: In this presentation, we will describe the organization of functional peptides as sidechains on polymer scaffolds as a new class of poly(peptide). We categorize these into two general classes; 1) Peptide-Polymer Amphiphiles (PPAs), which consist of block copolymers with a dense grouping of peptides arrayed as the sidechains of the hydrophilic block and connected to a hydrophobic block that drives micelle assembly, and 2) Protein-Like Polymers (PLPs), wherein peptide-brush polymers are composed from monomers, each containing a peptide side-chain. Peptides organized in this manner imbue polymers or polymeric nanoparticles with a range of functional qualities inherent to their specific sequence. Therefore, polymers or nanoparticles otherwise lacking bioactivity, or responsiveness to stimuli, once linked to a peptide of choice, can now bind proteins, enter cells and tissues, have controlled and switchable biodistribution patterns, and be enzyme substrates (e.g. for kinases, phosphatases, proteases). Indeed, where peptide substrates are incorporated, kinetically- or thermodynamically-driven morphological transitions can be enzymatically induced in the polymeric material. Synergistically, the polymer enforces changes in peptide activity and function by virtue of packing and constraining the peptide. The scaffold can protect the peptide from proteolysis, change the pharmacokinetic profile of an intravenously injected peptide, increase the cellular uptake of an otherwise cell impermeable therapeutic peptide, or change peptide substrate activity entirely. Moreover, in addition to the sequence-controlled peptides (generated by solid phase synthesis) the polymer can carry its own sequence-dependent information, especially through living polymerization strategies allowing well-defined blocks and terminal labels (dyes, contrast agents, charged moieties). Hence, the two elements, peptide and polymer, cooperate to yield materials with unique function and properties quite apart from each alone. Herein, we describe the development of synthetic strategies for accessing these classes of biomolecule polymer conjugates, and discuss their utility in a range of settings, including as a new class of peptide therapeutics.

Biography: Prof. Nathan C. Gianneschi received his B.Sc(Hons I) at the University of Adelaide, Australia in 1999. In 2005 he completed his Ph.D. at Northwestern University. Following a Dow Chemical postdoctoral fellowship at The Scripps Research Institute, in 2008 he began his independent career at the University of California, San Diego where, until June 2017, he was Teddy Traylor Scholar and Professor of Chemistry & Biochemistry, NanoEngineering and Materials Science & Engineering. In July of 2017, Gianneschi moved his research group to Northwestern University where he is currently Jacob & Rosaline Cohn Professor of Chemistry, Materials Science & Engineering, and Biomedical Engineering. The Gianneschi group takes an interdisciplinary approach to nanomaterials research with a focus on multifunctional materials with interests that include biomedical applications, programmed interactions with biomolecules and cells, and basic research into nanoscale materials design, synthesis and characterization. For this work he has been awarded the NIH Director’s New Innovator Award, the NIH Director’s Transformative Research Award and the White House’s highest honor for young scientists and engineers with a Presidential Early Career Award for Scientists and Engineers. Prof. Gianneschi was awarded a Dreyfus Foundation Fellowship, is a Kavli Fellow of the National Academy of Sciences, a Fellow of the Royal Society of Chemistry, and is an Alfred P. Sloan Foundation Fellow.

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