The incorporation of O-linked glycosides into endogenous neuropeptides provides glycopeptides of enhanced stability that penetrate the Blood-Brain Barrier (BBB), and retain affinity for their G-Protein Coupled Receptors (GPCRs). Several examples have been explored to produce analgesic and neuroprotective CNS drugs with masses ranging from 700—3,500 M.W., including enkephalins, endorphinsdynorphins, secretins and other potent peptide hormones. We may regard this class of drugs as one that bridges the gap between "small molecules" and "biologics."
Polt has embraced several relatively diverse scientific disciplines in his career, often running counter to the prevailing wisdom and advice. He studied chemistry at IUPUI under the direction of Prof. Martin J. O’Donnell, where he was involved in the enantioselective alkylation of masked glycine anion and cation equivalents to produce the first of the “O’Donnell Schiff Bases.” (Ph2C=O + H2NCH2CO2CH2CH3 → Ph2C=NCH2CO2CH2CH3) A NSF Fellowship that took him to Columbia University where he studied with Prof. Gilbert J. Stork, and then on to Prof. Dieter Seebach’s group in Zürich where he studied the alkylation of peptides in addition to glycine equivalents. Robin shifted his interests toward the synthesis and evaluation of glycopeptide drugs at the University of Arizona. Glycosylated neuropeptides show excellent biological activity, extended stability in vitro and in vivo, and also cross the blood-brain barrier to produce centrally-mediated effects. Presently, Robin is involved in the study of glycolipid surfactants in collaboration with Prof. Jeanne Pemberton, as well as Prof. Michael Heien, who uses MS2 and MS3 techniques coupled with microdialysis to quantify our drugs and their metabolites in vivo.