When
Presenter:
Hannah Goodman, PhD Candidate, Department of Chemistry and Biochemistry, The University of Arizona
Abstract:
xytocin is considered an essential medicine by the World Health Organization and clinically administered daily. It is a pleiotropic neurohormone conserved across species for 700 million years, inspiring scientists to apply it as a multifunctional therapeutic for a range of implicated dysfunctions. Yet its broader pharmaceutical application remains hindered by its pharmacology, especially its short half-life, minimal blood-brain barrier (BBB) penetration, and receptor promiscuity. The inability to make oxytocin a widely useful therapeutic despite over a century of clinical implementation is exemplary of the promise and limitations of peptide drugs. We applied common synthetic strategies for improving the “druggability” of peptide drugs (e.g., cyclization, glycosylation) to generate robust, BBB penetrant, receptor selective oxytocin analogues. Delivery of these and other glycopeptide candidates is probed by Pulsed field gradient Nuclear Magnetic Resonance (PFG-NMR) Spectroscopy data supplemented with data from in vivo, in vitro, and in silico studies. Glycolipid micelles are assessed as novel vehicles for delivering on the therapeutic promise of (glyco)peptide drugs.