title: A Selective Galactose-Coumarin-Derived Galectin-3 Inhibitor Demonstrates Involvement of Galectin-3-glycan Interactions in a Pulmonary Fibrosis Model.
abstract: Synthesis of doubly 3-O-coumarylmethyl-substituted thiodigalactosides from bis-3-O-propargyl-thiodigalactoside resulted in highly selective and high affinity galectin-3 inhibitors. Mutant studies, structural analysis, and molecular modeling revealed that the coumaryl substituents stack onto arginine side chains. One inhibitor displayed efficacy in a murine model of bleomycin-induced lung fibrosis similar to that of a known nonselective galectin-1/galectin-3 inhibitor, which strongly suggests that blocking galectin-3 glycan recognition is an important antifibrotic drug target.
authors: Indian Institute of Science Education and Research-Kolkata (IISER) Kolkata , Mohanpur Campus, P.O. BCKV Campus Main Office, Mohanpur, Nadia 741246, India.|Centre for Analysis and Synthesis, Department of Chemistry, Lund University , POB 124, SE-221 00 Lund, Sweden.
authors: Vishal K
authors: VK
authors: Rajput
authors: MRC Centre for Inflammation Research, The Queen's Medical Research Institute, University of Edinburgh , Edinburgh EH16 4TJ, U.K.
authors: Alison
authors: A
authors: MacKinnon
authors: Centre for Analysis and Synthesis, Department of Chemistry, Lund University , POB 124, SE-221 00 Lund, Sweden.
authors: Santanu
authors: S
authors: Mandal
authors: Institute for Glycomics, Griffith University , Gold Coast Campus, Parklands Southport, Queensland 4222, Australia.
authors: Patrick
authors: P
authors: Collins
authors: Institute for Glycomics, Griffith University , Gold Coast Campus, Parklands Southport, Queensland 4222, Australia.
authors: Helen
authors: H
authors: Blanchard
authors: Department of Laboratory Medicine, Section MIG, Lund University , BMC-C1228b, Klinikgatan 28, SE-221 84 Lund, Sweden.
authors: Hakon
authors: H
authors: Leffler
authors: Department of Respiratory Medicine and Allergy, Kings College , Denmark Hill Campus, Bessemer Road, London SE5 9RS, U.K.
authors: Tariq
authors: T
authors: Sethi
authors: Galecto Biotech ApS, COBIS , Ole Maaloes vej 3, Copenhagen N, DK-2200, Denmark.
authors: Hans
authors: H
authors: Schambye
authors: Indian Institute of Science Education and Research-Kolkata (IISER) Kolkata , Mohanpur Campus, P.O. BCKV Campus Main Office, Mohanpur, Nadia 741246, India.
authors: Balaram
authors: B
authors: Mukhopadhyay
authors: Centre for Analysis and Synthesis, Department of Chemistry, Lund University , POB 124, SE-221 00 Lund, Sweden.
authors: Ulf J
authors: UJ
authors: Nilsson
mesh_terms: D000818:Animals; D001761:Bleomycin; D003374:Coumarins / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D005697:Galactosides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D037502:Galectin 3 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D009154:Mutation; D011134:Polysaccharides / Q000378:metabolism*; D011485:Protein Binding; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D013329:Structure-Activity Relationship; D013862:Thiogalactosides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D003374:Coumarins; D005697:Galactosides; D037502:Galectin 3; D011134:Polysaccharides; D013862:Thiogalactosides; C000621129:bis-3,3'-((2H-1-benzopyran-2-on-3-yl)-1,1'-sulfanediyldigalactopyranoside; D001761:Bleomycin