Chemistry and Materials Science Seminar: Thioamides and Proteolysis

Chemistry and Materials Science Seminar
Thioamides and Proteolysis: Examining the Effects and Applications of a Single-atom Substitution

Dr. Taylor M. Barrett ’15
Medical Writer
Fishawack Health
RIT Chemistry BS Alumna ’15

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This seminar may be attended in person in 1174 Gosnell Hall or online via Zoom.

Can a single atom substitution in a biomolecule, such as a peptide or protein, really make that big of a difference? To find out, we examined the positional and stabilization effects of thioamides, an oxygen-to-sulfur substitution in the backbone of peptides and proteins, on model substrates and created a small library of stabilized peptides for imaging cancer cells.

Abstract:
Thioamide substitution in the peptide backbone enables several applications including studying proteolysis, monitoring protease activity, and selective protease inhibition. To date, we have used model substrates to investigate the positional effects that these thioamide substitutions have on proteolysis rates, as well as examining the ability of thioamides to stabilize peptides for imaging applications. In order to determine the positional effects of thioamides, we have examined several model peptides with a thioamide scanned from the P3 position to the P3' position and identified thioamide perturbing and non-perturbing positions. Further mechanistic investigation showed that the primary effect of the thioamide is often to prevent binding to the protease. Finally, incorporation of a thioamide into a peptide scaffold that is known to selectively bind to the neuropeptide Y Y1 receptor increased its serum stability, without affecting its affinity for the receptor. Currently, we are optimizing this stabilized imaging peptide usage in animals by changing linkers, fluorophores, and N-terminal modifications. We are also developing a system where full-length peptide hormones can be expressed, stabilized via thioamidation, and tagged with a fluorophore to afford in vivo peptide hormone imaging agents. Together, these studies provide guidelines for positioning thioamides for various proteolysis applications and show that thioamides can be used to create stabilized imaging peptides.

Speaker Bio:
Dr. Taylor M. Barrett graduated with her BS in Chemistry from RIT in 2015, after spending four wonderful years conducting research on multi-modal imaging agents in the Schmitthenner research lab. Next, she ventured to the University of Pennsylvania to complete her PhD in Chemistry under the guidance of Prof. E. James Petersson. Once she completed her PhD, Dr. Barrett did a brief stint as a Visiting Assistant Professor of Biochemistry at Swarthmore College, where she taught upper and advanced level biochemistry courses, including a seminar course. Now, Dr. Barrett is exploring the world of science outside of academia in her role as a medical writer at Fishawack Health. In this role, Dr. Barrett constructs numerous assets on the COVID-19 disease area, including medical science liaison training decks and educational webinar materials. During her talk, Dr. Barrett will discuss her graduate school research which focused on the introduction, effects, and applications of thioamide substitutions into the backbone of peptides and proteins.

Intended Audience:
Undergraduates, graduates, experts. Those with interest in the topic.

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