Cell-Surface Glycoconjugates III

University Of Arizona, Tucson AZ

Investigators

Abstract

With the support of the Organic AND Macromolecular Chemistry Program in the Chemistry Division, Professor Robin Polt, of the Chemistry Department at the University of Arizona, will focus on specific chemical goals of synthesis and biophysical characterization of glycopeptides that are designed to interact with membranes in ways similar to that of endogenous hormones normally found in the human brain. Studies of glycosylated and unglycosylated amphipathic alpha helices will be facilitated by the chemical synthesis of Fmoc-protected O-linked glycosyl-amino acids that can be incorporated into helical peptide sequences. By varying the relative amount and spatial distribution of the hydrophilic and hydrophobic surface areas of the helices, glycopeptides with different bilayer affinities can be created and studied by several biophysical methods. Classical solution H(1)-NMR protein methods for conformational analysis can be exploited in the presence of deuterated micelles and bicelles that mimic bilayer environments. Molecular mechanics (Monte Carlo methods) will be directed by nuclear Overhauser (NOE) data to understand the conformational ensembles of the glycopeptides as the environment is changed from aqueous (homogeneous media) to amphipathic (heterogeneous media). Solid-state H(2)-NMR and N(15)-NMR methods will be used to observe the orientation of glycopeptides helices with respect to oriented lipid bilayers, as well as to observe their effect on bilayer structure. Based on the observed structures, hydrophilic and hydrophobic surface areas will be calculated. With the support of the Organic Dynamics Program in the Chemistry Division, Professor Polt will examine interaction of glycopeptides with membrane bilayers, which is not well studied, but is likely to impact the understanding of such diverse biological phenomena as the interaction of peptide/glycopeptide hormones and neurotransmitters with receptors, display of peptide antigens, and mechanisms of viral entry. Broader Impacts resulting from the proposed activity include the training of graduate, undergraduate and post-graduate researchers from diverse cultural and ethnic backgrounds. Presently, the Polt Group represents an international and multicultural environment, consisting of male and female graduate, undergraduate, and post-graduate students from Korea, Kenya, Ireland, Mexico and China, as well as from the United States. Students participate in every aspect of research, including the laboratory work, writing and presentation of papers and proposals, participating in international scientific meetings and conferences, as well as in the training of undergraduates and other graduate students. Students have won awards at the departmental, university and national levels for their research work from NSF (Fellowships), the Goldwater Foundation, Galileo Circle, McNair Fellowship, and the ARCS Foundation.