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Synthesis and Characterization of Clickable Polyproline Based Materials

Year: 2023

Presenter Name: Clara Coffey

Mucus, collagen, and proteoglycans serve crucial roles in the human body, yet current research on these structures is limited. Mucus is the interface and first line of defense to the world around us; it lubricates and hydrates epithelial surfaces, houses the microbiome, and allows for the diffusion of drugs and nutrients while trapping pathogens by acting as a selectively permeable membrane. Mucus is a hydrogel made primarily of water and ions and is 5-9wt% glycoproteins, known as mucins. These mucins are characterized by high molecular weight repeat domains rich in proline and O-glycosylated serine and threonine (PTS domains). Proline, an amino acid contributing to the rigidity of proteins, possesses unique properties in mucus, collagen, and proteoglycans. Despite polyproline-based materials having additional applications including surface coatings, hydrogels, antithrombotics, as ordered materials, and in probing protein structure, current mucin research is limited to reconstituted mucins, often from intestinal scrapings of farm animals. These glycoproteins vary greatly between samples in both structure and chemistry due to inherent heterogeneity in mucins between species, tissues, and pathologies. In response, we have synthesized the building blocks of proline-based mucin, collagen, and proteoglycan mimics working towards allowing for the modeling of mucins and mucus, structure-function relationships, related diseases, and novel lubricating therapeutics. Through N-carboxyanhydride polymerization, we have synthesized three proline analog polypeptides. These analogs support the exploration of simpler materials to create a synthetic PTS domain and capture hydrophilic PPII structure. Our findings will be advantageous in next steps exploring azide-alkyne cycloaddition "click" reactions of these proline analogs with sugars in exploring structure-function relationships, the contributions of individual amino acid residues, and sugar and glycan patterns in mucin function.
University / Institution: University of Utah
Type: Oral
Format: In Person
SESSION A (9:00-10:30AM)
Area of Research: Engineering
Faculty Mentor: Jessica Kramer
Location: Alumni House, HENRIKSEN ROOM (9:00am)