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Title: New Synthetic Tools for Peptide Medicinal Chemistry
Abstract: 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.
Presenter: Dr. Steven Bloom , University of Kansas
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 doctoral studies with Prof. Thomas Lectka, studying synthetic organofluorine chemistry and catalysis. After graduation, Steve traveled to Princeton University (2015-2018) to complete postdoctoral studies with Prof. David MacMillan as an NIH Ruth L. Kirschstein fellow. In the MacMillan lab, Steve worked in bioorganic chemistry, developing new photocatalytic methods to site-specifically functionalize native 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 strategic diversification of peptides, with a focus on unnatural amino acid incorporation. The Bloom lab uses these methods to pioneer several medicinal chemistry projects in various disease areas, including HIV-1, monogenic obesity, and ischemic stroke.
Dr. Bloom is a recipient of an NIH NIGMS R35 MIRA award and an NIH NIGMS P20 grant. He was also the recipient of a 2021 Thieme Chemistry Journal award, in recognition of his original contributions to chemical catalysis and the creation of new synthetic methods. Finally, Dr. Bloom was the recipient of the 2021 University of Kansas teacher of excellence award for his efforts in undergraduate medicinal chemistry education.
Hosted by: Dr. Wei Wang