Polysaccharides are known to module the native conformation and stability of large globular proteins in many biological systems. Similar effects leading to drastic changes on biological activity can ...always be observed when simple carbohidrates are chemically bound to small peptide ligands. Opioid peptides are a good exam¬ple of dramatic activity potentiation by glicosidation. To inves¬tigate if similar phenomena take place on the opioid receptor like (ORL) ligand, nociceptin, four glycopeptide analogs of this heptadecapetide have been synthesized. Thus, an O alfa D GalNAc and a O beta D GlcNAc on Ser10, an O alfa D GalNAc on Thr5 and a Lac on (Ser Thr) substituted nociceptin analogues, were prepared. Their binding affinity for the ORL have been determined on HEK‐293 cells stably expressing the zefrafish ORL receptor. Moreover, their solution conformation has been studied by circular dicro¬ism, NMR spectroscopy and molecular mechanics and dynamics calcu¬lations. A discussion of activity conformation relationships features on this glycopeptides will be presented.
This research was supported by LA MARATO TV3 from the Regional Government of Cataluña.
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