Synthetic, structural and biological studies on glycosylated amphiphilic polyproline II helices

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This proposed research program focuses on the creation and characterization of preorganized natural and unnatural polyproline-based (glyco)peptide scaffolds with the ability to mimic the functional and biological properties of complex structural proteins of the plant- and animal kingdom. In the short-term we will prepare and study the structural properties of functionalized amphiphilic polyproline II mono helices with single, double or triple amphiphilic faces designed to mimic the functions of plant-based structural proteins [project A]. In a second project we will prepare and study the self-assembling and structural properties of amphiphilic polyproline triple helices designed to mimic the functional properties of collagens [project B]. Access to well-defined, homogeneous plant- and animal-inspired structural protein mimetics provides an indispensable tool to study the poorly-understood molecular recognition events at the extracellular matrix of plants and mammalian cells. This approach overcomes current limitations in protein expression that result in heterogeneous mixtures with little control over post-translational modifications such as glycosylation. In the longer-term we will explore the use of these peptide scaffolds in cell delivery but also as therapeutic devices with antibacterial, antitumor and immunomodulatory properties in medicine and artificial tissue engineering. Moreover, this study will address existing gaps in our knowledge how glycosylation affects the structure and functions of structural proteins in living organisms and how helical chirality affects the structural and biological properties of the polyproline single- and triple helix. Existing collaborations with researchers at the Faculty of Medicine at UofM as well as new collaborations with material chemists at the Manitoba Institute for Materials will be used to train students in a unique multidisciplinary research environment ranging from Organic Chemistry, Medicinal Chemistry, Glycobiology, Microbiology, Cancer Research, Immunology to Materials Science. Students involved in these studies will be uniquely trained and highly desirable in the biopharmaceutical and biotechnology sectors of the Canadian economy.