Double Affinity Amplification of Galectin-Ligand Interactions through Arginine-Arene Interactions: Synthetic, Thermodynamic, and Computational Studies with Aromatic Diamido-Thiodigalactosides.

Summary, in English

A series of aromatic mono- or diamido-thiodigalactoside derivatives were synthesized and studied as ligands for galectin-1, -3, -7, -8N terminal domain, and -9N terminal domain. The affinity determination in vitro with competitive fluorescence-polarization experiments and thermodynamic analysis by isothermal microcalorimetry provided a coherent picture of structural requirements for arginine-arene interactions in galectin-ligand binding. Computational studies were employed to explain binding preferences for the different galectins. Galectin-3 formed two almost ideal arene-arginine stacking interactions according to computer modeling and also had the highest affinity for the diamido-thiodigalactosides (K(d) below 50 nM). Site-directed mutagenesis of galectin-3 arginines involved in binding corroborated the importance of their interaction with the aromatic diamido-thiodigalactosides. Furthermore, the arginine mutants revealed distinct differences between free, flexible, and solvent-exposed arginine side chains and tightly ion-paired arginine side chains in interactions with aromatic systems.

• Författare: Ian Cumpstey; Emma Salomonsson; Anders Sundin; Hakon Leffler; Ulf Nilsson
• Avdelning/ar: Centrum för analys och syntes; Avdelningen för mikrobiologi, immunologi och glykobiologi - MIG
• Publiceringsår: 2008
• Språk: Engelska
• Sidor: 4233-4245
• Publikation/Tidskrift/Serie: Chemistry: A European Journal
• Volym: 14
• Issue: 14
• Länkar: http://www.ncbi.nlm.nih.gov/pubmed/18366047?dopt=Abstract; http://dx.doi.org/10.1002/chem.200701932
• Dokumenttyp: Artikel i tidskrift
• Förlag: Wiley-Blackwell
• Ämne: Microbiology in the medical area; Immunology in the medical area
• Nyckelord: carbohydrates; galectin; inhibitors; thioglycosides
• Status: Published
• ISBN/ISSN/Övrigt: ISSN: 1521-3765