CARBOHYDRATE AND GLYCOPEPTIDE INTERACTIONS WITH LECTINS

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Carbohydrates on the surface of both normal and transformed cells function as receptor determinants in various biological recognition processes. Three classes of these covalently bound molecules are called high mannose, complex, and hybrid type oligosaccharides, which each form a variety of structures. Although they function as cell surface receptors, little is known of the molecular binding properties of these oligosaccharides, other than they are substrates for glycosylases, and that they bind to lectins. Lectins are plant and animal proteins which bind to specific carbohydrate determinants without modifying them. Plant lectins have a wide number of biological applications, including their use in exploring the structure and dynamic properties of the membranes of normal and transformed cells. Among the more widely employed plant metallolectins are Concanavalin A (Con A), and the lentil (LcH), pea (PSA), soybean (SBA) and lima-bean (LBL) lectins, all of which possess different binding specificities, and a range of different biological activities. Our objectives are to determine the molecular binding mechanisms of high mannose complex, and hybrid type glycopeptides and related synthetic oligosaccharides with lectins in order to investigate the molecular recognition determinants of these cell surface receptors. The spectroscopic properties of the lectins including their bound metal ions will be investigated, since the metal ions can serve as intrinsic reporter groups for monitoring the interactions of the carbohydrates with the proteins. Our discovery of a method of preparing metal ion derivatives of LcH and PSA now makes in possible to study the interactions of these two lectins, in addition to the other lectins, with the carbohydrates by a variety of spectroscopic techniques, including nuclear magnetic resonance (NMR), electron spin resonance (EPR) and spin-echo, and circular dichroism (CD) measurements. NMR techniques will include solvent proton NMR dispersion measurements, and high resolution 1H, 19F, 13C, and 113Cd NMR experiments. These studies will provide direct data on the molecular binding properties of these important classes of cell surface carbohydrates, as well as the binding specificities of the lectins.