About the Seminar:

While the use of small organic molecules as therapeutic agents (drugs) goes back to antiquity, the therapeutic use of peptide drugs is a very recent phenomenon. Approximately 60 peptides have been introduced for clinical use in the past 25 years. 85% of these peptides contain at least one non-proteinogenic amino acid—those outside of the naturally encoded and translated amino acids—to confer metabolic stability, receptor potency and/or receptor selectivity to the peptide. Finding the optimal residue involves trial and error, each variant peptide being made as the unique product of a long, tedious, and chemically inefficient Solid Phase Peptide Synthesis (SPPS) procedure. We introduce a radically new approach to greatly accelerate the discovery process. Our approach takes advantage of a naturally encoded ‘pro-amino acid’, dehydroalanine, as a chemical lynchpin. Implanted into ordinary peptides, dehydroalanine can become one of any number of non-proteinogenic residues by reaction with one- or two- electron nucleophiles. Applied in parallel formats, entirely new libraires of peptides that address new therapeutic targets can be made, purified, quantified, and biochemically tested.

About the Speaker:

Steve is a native of Baltimore, Maryland. He attended McDaniel College (2006-2010) where he earned his B.A. in chemistry and biochemistry. During this time, Steve completed summer research at the Aberdeen Proving Ground and Edgewood Chemical & Biological Command. He then moved to Johns Hopkins University (2010-2015) to complete his doctoral studies with Prof. Thomas Lectka, studying synthetic organofluorine chemistry and catalysis. After graduation, Steve traveled to Princeton University (2015-2018) to complete his postdoctoral studies with Prof. David MacMillan as an NIH fellow. In the MacMillan lab, Steve worked in bioorganic chemistry, developing new photocatalytic methods to site-specifically functionalize peptides and proteins. Steve began his independent career at the University of Kansas in 2018 and his group is currently developing new synthetic chemistries for the diversification of peptides. The Bloom lab uses these methods to pioneer several medicinal chemistry projects in various disease areas.