Polt Group HomePage Publications Curriculum Vitae Send eMail Telephone: (520) 621-6322 FAX: (520) 621-8407 polt@u.arizona.edu

Cell-surface carbohydrates (glycoproteins & glycolipids) have achieved a prominent place during the past decade, giving rise to the new discipline of "glycobiology." Cell-surface carbohydrates play decisive roles during mammalian fertilization, embryogenesis, normal cellular differentiation and regulation, as well as critical roles in malignancy, tumor growth, and tumor cell metastasis. The vertebrate nervous system seems to be a special beneficiary of the cell-cell communication afforded by glycoconjugates, and we are especially interested in the synthesis of ganglioside analogues which may be useful in probing neuronal development, the formation of synapses, and tumor cell metastasis.

The influence of the carbohydrate moiety on glycoprotein structure and function is an area of interest to the "Polt Group." Using synthetic methods developed in our laboratory, the preferred conformations of various glycopeptide model systems are being determined using state-of-the-art 2-D NMR techniques. This data will permit glycobiologists to understand intracellular trafficking and intercellular transport of glycoproteins at the molecular level. Work done by the "Polt Group" in collaboration with the "Hruby Group" has produced glycopeptide analogues of neurotransmitters which are capable of crossing the blood-brain barrier. These are the first peptide-based chemicals to function as drugs in vivo.

New synthetic methodology developed in the "Polt Group" is focused on the use of metal-ligand interactions to direct C-C and C-O bond formations starting from amino acids, such as L-alanine and D-serine. These new methods are being applied to the synthesis of highly-functionalized natural products such as castanospermine which functions as a glycosidase inhibitor, or to unnatural substrate analogues designed to inhibit glycoprotein processing enzymes (glycosyltransferases).

Selected Publications

"Amyryllidacease Alkaloids with Anti-tumor Activity". Org. Synth; Theory Appl., 3, 109-148 (1996).

"General Methods for - or -O-Ser-/Thr Glycosides and Glycopeptides. Solid Phase Synthesis of O-Glycosyl Cyclic Enkephalin Analogues." Robin Polt, Lajos Szabò, Jennifer Treiberg, Yushun Li, and Victor J. Hruby, Journal of the American Chemical Society, 114, 10249-58 (1992).

"N-Diphenylmethylene-Protected Glycosyl Acceptors. Selective -O-Glycosylation to Form Lactosyl-threo-Ceramides." Matt A. Peterson and Robin Polt, Journal of Organic Chemistry, 58, 4309-14 (1993).

"An Enantioselective synthesis of N-Methyl Fucosamine via Tandem C-C/C-O Bond Formation." Dalibor Sames and Robin Polt, Journal of Organic Chemistry, 59, 4596-4601 (1994).

"Piperidine Triols via Enantioselective Alkylation and Osmylation of Alanine Schiff Base Esters." Dalibor Sames and Robin Polt, SYNLETT, 552-4 (1995).

"Glycopeptide enkephalin analogues produce analgesia in mice: Evidence for penetration of the blood-brain barrier." Robin Polt, Victor Hruby, et al, Proceedings of the National Academy of Sciences, USA, 91, 7114-8 (1994).

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