title: Alpha-O-linked glycopeptide mimetics: synthesis, conformation analysis, and interactions with viscumin, a galactoside-binding model lectin.
abstract: Efficient cycloaddition of a silylidene-protected galactal with a suitable heterodiene yielded the basis for a facile diastereoselective route to a glycopeptide-mimetic scaffold. Its carbohydrate part was further extended by beta1-3-linked galactosylation. The pyranose rings retain their (4)C(1) chair conformation, as shown by molecular modeling and NMR spectroscopy, and the typical exo-anomeric geometry was observed for the disaccharide. The expected bioactivity was ascertained by saturation-transfer-difference NMR spectroscopy by using the galactoside-specific plant toxin viscumin as a model lectin. The experimental part was complemented by molecular docking. The described synthetic route and the strategic combination of computational and experimental techniques to reveal conformational properties and bioactivity establish the prepared alpha-O-linked glycopeptide mimetics as promising candidates for further exploitation of this scaffold to give O-glycans for lectin blocking and vaccination.
authors.affiliation: Chemical and Physical Biology, Centro de Investigaciones Biológicas, CSIC, Ramiro de Maeztu 9, 28040 Madrid, Spain. jjbarbero@cib.csic.es
authors.forename: Jesús
authors.initials: J
authors.lastname: Jiménez-Barbero
authors.forename: Elisa
authors.initials: E
authors.lastname: Dragoni
authors.forename: Chiara
authors.initials: C
authors.lastname: Venturi
authors.forename: Federico
authors.initials: F
authors.lastname: Nannucci
authors.forename: Ana
authors.initials: A
authors.lastname: Ardá
authors.forename: Marco
authors.initials: M
authors.lastname: Fontanella
authors.forename: Sabine
authors.initials: S
authors.lastname: André
authors.forename: Francisco Javier
authors.initials: FJ
authors.lastname: Cañada
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Gabius
authors.forename: Cristina
authors.initials: C
authors.lastname: Nativi
mesh_terms: D015195:Drug Design; D006020:Glycopeptides / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D015394:Molecular Structure; D011487:Protein Conformation; D054790:Ribosome Inactivating Proteins, Type 2 / Q000737:chemistry* / Q000302:isolation & purification; D013237:Stereoisomerism; D014118:Toxins, Biological / Q000737:chemistry* / Q000302:isolation & purification
chemical_list: D006020:Glycopeptides; D054790:Ribosome Inactivating Proteins, Type 2; D014118:Toxins, Biological; C488862:mistletoe lectin I