Fluorinated Carbohydrates as Lectin Ligands: 19F-Based Direct STD Monitoring for Detection of Anomeric Selectivity

Biomolecules

João P. Ribeiro³  Tammo Diercks⁴  Jesús Jiménez-Barbero⁴  Sabine André²  Hans-Joachim Gabius²  Francisco Javier Ca󱫚¹ 

[1] Chemical and Physical Biology, Centro de Investigaciones Biológicas, CIB-CSIC, Ramiro de Maeztu 9, 28040 Madrid, Spain;Institut für Physiologische Chemie, Tierärztliche Fakultät der Ludwig-Maximilians-Universität, Veterinärstr. 13, 80539 München, Germany; E-Mail:;Centre de Recherches sur les Macromolécules Végétales, UPR5301, CNRS-Université Grenoble Alpes, BP53, 38041 Grenoble cédex 09, France; E-Mail:;CIC bioGUNE, Bizkaia Technological Park, Building 800, 48160 Derio, Spain; E-Mail:

关键词: agglutinin;    carbohydrates;    drug design;    glycans;    glycoproteins;    lectins;    sugar receptors;   

DOI  :  10.3390/biom5043177

来源: mdpi

【 摘 要 】

The characterization of the binding of reducing carbohydrates present as mixtures of anomers in solution to a sugar recepor (lectin) poses severe difficulties. In this situation, NMR spectroscopy enables the observation of signals for each anomer in the mixture by applying approaches based on ligand observation. Saturation transfer difference (STD) NMR allows fast and efficient screening of compound mixtures for reactivity to a receptor. Owing to the exceptionally favorable properties of ¹⁹F in NMR spectroscopy and the often complex ¹H spectra of carbohydrates, ¹⁹F-containing sugars have the potential to be turned into versatile sensors for recognition. Extending the recently established ¹H → ¹H STDre¹⁹F-NMR technique, we here demonstrate its applicability to measure anomeric selectivity of binding in a model system using the plant lectin concanavalin A (ConA) and 2-deoxy-2-fluoro-d-mannose. Indeed, it is also possible to account for the mutual inhibition between the anomers on binding to the lectin by means of a kinetic model. The monitoring of ¹⁹F-NMR signal perturbation disclosed the relative activities of the anomers in solution and thus enabled the calculation of their binding affinity towards ConA. The obtained data show a preference for the α anomer that increases with temperature. This experimental approach can be extended to others systems of biomedical interest by testing human lectins with suitably tailored glycan derivatives.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.