title: Conformational Plasticity in Glycomimetics: Fluorocarbamethyl-L-idopyranosides Mimic the Intrinsic Dynamic Behaviour of Natural Idose Rings.
abstract: Sugar function, structure and dynamics are intricately correlated. Ring flexibility is intrinsically related to biological activity; actually plasticity in L-iduronic rings modulates their interactions with biological receptors. However, the access to the experimental values of the energy barriers and free-energy difference for conformer interconversion in water solution has been elusive. Here, a new generation of fluorine-containing glycomimetics is presented. We have applied a combination of organic synthesis, NMR spectroscopy and computational methods to investigate the conformational behaviour of idose- and glucose-like rings. We have used low-temperature NMR spectroscopic experiments to slow down the conformational exchange of the idose-like rings. Under these conditions, the exchange rate becomes slow in the (19) F NMR spectroscopic chemical shift timescale and allows shedding light on the thermodynamic and kinetic features of the equilibrium. Despite the minimal structural differences between these compounds, a remarkable difference in their dynamic behaviour indeed occurs. The importance of introducing fluorine atoms in these sugars mimics is also highlighted. Only the use of (19) F NMR spectroscopic experiments has permitted the unveiling of key features of the conformational equilibrium that would have otherwise remained unobserved.
authors.affiliation: Chemical and Physical Biology Department, Centro de Investigaciones Biológicas, CIB-CSIC, Ramiro de Maeztu 9, 28040 Madrid (Spain).|Infectious Disease Programme, CIC bioGUNE, 48160 Derio, Bizkaia (Spain).
authors.forename: Luca
authors.initials: L
authors.lastname: Unione
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, Institut Universitaire de France, UMR CNRS 8232, IPCM, 4, place Jussieu, 75005 Paris (France).|Present address: The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, 202 Shachong South Road, Guiyang, 550002 (P. R. China).
authors.forename: Bixue
authors.initials: B
authors.lastname: Xu
authors.affiliation: Chemical and Physical Biology Department, Centro de Investigaciones Biológicas, CIB-CSIC, Ramiro de Maeztu 9, 28040 Madrid (Spain).
authors.forename: Dolores
authors.initials: D
authors.lastname: Díaz
authors.affiliation: Chemical and Physical Biology Department, Centro de Investigaciones Biológicas, CIB-CSIC, Ramiro de Maeztu 9, 28040 Madrid (Spain).
authors.forename: Sonsoles
authors.initials: S
authors.lastname: Martín-Santamaría
authors.affiliation: Infectious Disease Programme, CIC bioGUNE, 48160 Derio, Bizkaia (Spain).
authors.forename: Ana
authors.initials: A
authors.lastname: Poveda
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, Institut Universitaire de France, UMR CNRS 8232, IPCM, 4, place Jussieu, 75005 Paris (France).|Centro de Química e Bioquímica, Faculdade de Ciências da Universidade de Lisboa, Edifício C8, 1749-016 Lisboa (Portugal).
authors.forename: João
authors.initials: J
authors.lastname: Sardinha
authors.affiliation: Centro de Química e Bioquímica, Faculdade de Ciências da Universidade de Lisboa, Edifício C8, 1749-016 Lisboa (Portugal).
authors.forename: Amelia Pilar
authors.initials: AP
authors.lastname: Rauter
authors.affiliation: Université de Poitiers, UMR CNRS 7285, IC2MP, Equipe Synthèse organique, Groupe Glycochimie, 4, avenue Michel Brunet, 86022 Poitiers Cedex (France).
authors.forename: Yves
authors.initials: Y
authors.lastname: Blériot
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, Institut Universitaire de France, UMR CNRS 8232, IPCM, 4, place Jussieu, 75005 Paris (France).
authors.forename: Yongmin
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Chemical and Physical Biology Department, Centro de Investigaciones Biológicas, CIB-CSIC, Ramiro de Maeztu 9, 28040 Madrid (Spain).
authors.forename: F Javier
authors.initials: FJ
authors.lastname: Cañada
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, Institut Universitaire de France, UMR CNRS 8232, IPCM, 4, place Jussieu, 75005 Paris (France). matthieu.sollogoub@upmc.fr.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Sollogoub
authors.affiliation: Chemical and Physical Biology Department, Centro de Investigaciones Biológicas, CIB-CSIC, Ramiro de Maeztu 9, 28040 Madrid (Spain). jjbarbero@cicbiogune.es.|Infectious Disease Programme, CIC bioGUNE, 48160 Derio, Bizkaia (Spain). jjbarbero@cicbiogune.es.|IKERBASQUE, Basque Foundation for Science, 48011 Bilbao (Spain). jjbarbero@cicbiogune.es.
authors.forename: Jesus
authors.initials: J
authors.lastname: Jiménez-Barbero
mesh_terms: D001685:Biological Factors / Q000737:chemistry*; D005461:Fluorine / Q000737:chemistry*; D006601:Hexoses / Q000737:chemistry* / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D019906:Nuclear Magnetic Resonance, Biomolecular; D013816:Thermodynamics
chemical_list: D001685:Biological Factors; D006601:Hexoses; C010997:idose; D005461:Fluorine
keywords: L-idose; NMR spectroscopy; carbasugars; conformational equilibrium; fluorine