University of Arizona
Minimally Competent Lewis Acids: Effective and Efficient Catalysts for β-Glycosylation of Peptide Hormones
Dr. Elizabeth Schram YI Oral Competition
Wednesday, June 28, 2023, at 10:50 am -11:05 am
The synthesis of amino acid glycosides has been an ongoing synthetic challenge. Glycosylation of peptides has been shown to be an important way to enhance stability and transport of peptide- based drugs. Unfortunately, there are no universal conditions for the variety of glycosyl donors and acceptors commonly used, and the donors typically used are unstable.
Previous methods often require lengthy synthetic routes, unstable reagents, and low temperatures to provide the required glycosides.1, 2 This study examines the use of minimally competent Lewis acids, MCLAs, as robust catalysts for β-glycosylation of serine using stable sugar peracetates with the goal of developing more finely tuned catalysts for glycopeptides and other types of glycosides.
Troy Smith graduated from Millersville University of Pennsylvania with an honors degree, BSc, in Chemistry and a minor in Biology. During his tenure in Pennsylvania, he researched N-Heterocyclic Carbene catalysis under the direction of Dr. Edward Rajaseelan as well as developed new methodologies for the study of oil and grease at MRG Laboratories. Attending the University of Arizona as a George Gregson Scholar, Troy is pursuing his doctorate in chemistry under Dr. Robin Polt studying glycopeptides for the treatment of neurodegenerative diseases.
Troy's research focuses on how Neurodegenerative Disorders, ND, such as Alzheimer’s and Parkinsons negatively impact the lives of over 1 in every 50 people in the United States today. Despite the vast effect these diseases have on society, current therapeutics provide no curative effects, and only provide quality of life improvements to patients by mitigating symptoms as the disease progresses. Pituitary adenylate cyclase-activating polypeptide, PACAP, represents a potential drug candidate feedstock uniquely suited for treatments of neurodegenerative disorders due to the neuroprotective effects exhibited by binding to its target receptors, PAC1, VPAC1 and VPAC2.
While the native peptide is hampered by the poor in vivo pharmacokinetics, limited membrane permeability and low oral bioavailability that is characteristic of most peptides, Troy's research has seen significant success improving these characteristics through synthesis of glycopeptide PACAP analogues. Glycopeptide analogues of PACAP have shown improved Blood Brain Barrier, BBB, penetration and increased neuroprotective effects. My future goal is expanding on these methodologies to produce more effective and selective PACAP glycopeptide analogues for therapeutic treatments for Parkinson’s, Alzheimer’s, CTE and other conditions resulting from neurodegeneration.