Peptide Brush Polymers: Theory and Synthesis for Functional Design

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Nontechnical Summary This award by the Biomaterials program in the Division of Materials Research to Northwestern University is for the development of an approach to make peptide biomaterials into therapeutics and tools for discovery in biology. Peptides are typically small biomolecules discovered as fragments of proteins or coming from natural sources such as hormones. They are a class of molecule used to treat diseases such as diabetes. However, widespread use across diverse diseases has been severely limited compared to how many peptides are known. The promise of peptide biomaterials has also been limited because of several conspiring attributes. One is that, in using these molecules we are trying to make functional therapeutics out of that which we normally regard as food. Natural digestion processes break down peptides to amino acids before they can function. In addition, cells and tissues have physical barriers that prevent most foreign peptides from entering; an evolutionary feature that usually serves us well. These processes mean that peptides are short lived when given intravenously or orally as medicines. In addition, unlike large proteins such as antibodies, individual peptides lack the ability to make multiple contacts with target receptors that may be present on cells or invading pathogens. This is analogous to the difference between picking up a pen with one finger versus using an entire hand. We term this multivalency in target binding. This award focuses on the experimental and theoretical development of a new kind of peptide biomaterial formulation. These formulations display peptides at exceptionally high-density, enabling resistance to degradation, while maintaining and enhancing cell uptake and receptor binding, or gripping strength by multivalency. Through this effort to impact scientific problems of urgency and relevance to society, the award will establish a research internship for underrepresented post-baccalaureate students in science, to recruit them to STEM fields. The award will also enable outreach programs including one focused on clinicians interested in learning about future technologies of potential translational relevance arising from the fields of polymer chemistry and nanoscience.Technical Summary: Peptides show tremendous potential as therapeutics and as tools in chemical biology. However, this promise has been consistently compromised by natural digestion processes and by chemical and physical barriers in cells and tissues. These processes mean that peptides suffer from short half-lives upon systemic (intravenous or oral) administration and are degraded or excluded entirely from cells and organs. In addition, they can be low molecular weight as individual strands, a feature contributing to rapid clearance when administered systemically and to a lack of multivalency in target binding. This award focuses on the experimental and theoretical development of polymer scaffolds that are capable of displaying peptides at exceptionally high density enabling resistance to degradation, while maintaining and enhancing cell uptake and bioactivity. Furthermore, the project offers opportunities for broader societal impact. This is based on the fact that peptides are exciting targets, ripe for development with new delivery methods for longstanding, and for emerging diseases alike. To fuel these scientific thrusts, the program has established a research internship for underrepresented post-baccalaureate students in science to prepare them to apply for graduate school. The multidisciplinary research program seeks to broaden the base of students coming into STEM fields by recruiting them to work on scientific problems of urgency and relevance to society.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.