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α‐ O ‐Linked Glycopeptide Mimetics: Synthesis, Conformation Analysis, and Interactions with Viscumin, a Galactoside‐Binding Model Lectin
Author(s) -
JiménezBarbero Jesús,
Dragoni Elisa,
Venturi Chiara,
Nannucci Federico,
Ardá Ana,
Fontanella Marco,
André Sabine,
Cañada Francisco Javier,
Gabius HansJoachim,
Nativi Cristina
Publication year - 2009
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200901077
Subject(s) - glycopeptide , chemistry , lectin , pyranose , stereochemistry , disaccharide , galactoside , docking (animal) , scaffold , anomer , nuclear magnetic resonance spectroscopy , molecular model , biochemistry , enzyme , medicine , nursing , biomedical engineering , antibiotics
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 β1–3‐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 α‐ O ‐linked glycopeptide mimetics as promising candidates for further exploitation of this scaffold to give O ‐glycans for lectin blocking and vaccination.