Hakon Leffler

Summary

Affiliation: Lund University
Country: Sweden

Publications

  1. ncbi request reprint Introduction to galectins
    Hakon Leffler
    Section MIG Microbiology, Immunology, Glycobiology, Inst Laboratory Medicine, Lund University, Sweden
    Glycoconj J 19:433-40. 2004
  2. ncbi request reprint Dendritic cell maturation results in pronounced changes in glycan expression affecting recognition by siglecs and galectins
    Marieke Bax
    Department of Molecular Cell Biology and Immunology, Vrije Universiteit University Medical Center, Amsterdam, The Netherlands
    J Immunol 179:8216-24. 2007
  3. doi request reprint Different fractions of human serum glycoproteins bind galectin-1 or galectin-8, and their ratio may provide a refined biomarker for pathophysiological conditions in cancer and inflammatory disease
    Michael C Carlsson
    Section MIG Microbiology, Immunology, Glycobiology, Department of Laboratory Medicine, Lund University, Lund, Sweden
    Biochim Biophys Acta 1820:1366-72. 2012
  4. pmc Ligand induced galectin-3 protein self-association
    Adriana Lepur
    Microbiology, Immunology, and Glycobiology MIG Section, Department of Laboratory Medicine, Lund University, 223 62 Lund, Sweden
    J Biol Chem 287:21751-6. 2012
  5. pmc The carbohydrate-binding site in galectin-3 is preorganized to recognize a sugarlike framework of oxygens: ultra-high-resolution structures and water dynamics
    Kadhirvel Saraboji
    Department of Biochemistry and Structural Biology, Center for Molecular Protein Science, Box 124, Lund University, SE 221 00 Lund, Sweden
    Biochemistry 51:296-306. 2012
  6. ncbi request reprint Protein subtype-targeting through ligand epimerization: talose-selectivity of galectin-4 and galectin-8
    Christopher T Oberg
    Organic Chemistry, Lund University, PO Box 124, SE 221 00 Lund, Sweden
    Bioorg Med Chem Lett 18:3691-4. 2008
  7. doi request reprint Monovalent interactions of galectin-1
    Emma Salomonsson
    Institute of Laboratory Medicine, Lund University, Lund, Sweden
    Biochemistry 49:9518-32. 2010
  8. doi request reprint Arginine binding motifs: design and synthesis of galactose-derived arginine tweezers as galectin-3 inhibitors
    Christopher T Oberg
    Organic Chemistry, Lund University, SE 221 00 Lund, Sweden
    J Med Chem 51:2297-301. 2008
  9. pmc Galectin-1-binding glycoforms of haptoglobin with altered intracellular trafficking, and increase in metastatic breast cancer patients
    Michael C Carlsson
    Section Microbiology, Immunology, Glycobiology, Department of Laboratory Medicine, Lund University, Lund, Sweden
    PLoS ONE 6:e26560. 2011
  10. doi request reprint Double affinity amplification of galectin-ligand interactions through arginine-arene interactions: synthetic, thermodynamic, and computational studies with aromatic diamido thiodigalactosides
    Ian Cumpstey
    Organic Chemistry, Lund University, POB 124, 22100 Lund, Sweden
    Chemistry 14:4233-45. 2008

Collaborators

Detail Information

Publications43

  1. ncbi request reprint Introduction to galectins
    Hakon Leffler
    Section MIG Microbiology, Immunology, Glycobiology, Inst Laboratory Medicine, Lund University, Sweden
    Glycoconj J 19:433-40. 2004
    ..Here we will give a brief introduction to the galectins as a protein family with some comments on nomenclature...
  2. ncbi request reprint Dendritic cell maturation results in pronounced changes in glycan expression affecting recognition by siglecs and galectins
    Marieke Bax
    Department of Molecular Cell Biology and Immunology, Vrije Universiteit University Medical Center, Amsterdam, The Netherlands
    J Immunol 179:8216-24. 2007
    ..Interestingly, the binding of the LacNAc-specific lectins galectin-3 and -8 increased during maturation and up-regulation of sialic acid expression by mDC correlated with an increased binding of siglec-1, -2, and -7...
  3. doi request reprint Different fractions of human serum glycoproteins bind galectin-1 or galectin-8, and their ratio may provide a refined biomarker for pathophysiological conditions in cancer and inflammatory disease
    Michael C Carlsson
    Section MIG Microbiology, Immunology, Glycobiology, Department of Laboratory Medicine, Lund University, Lund, Sweden
    Biochim Biophys Acta 1820:1366-72. 2012
    ..Now we have explored the use of a combination of two galectins with different specificities, to further increase biomarker sensitivity and specificity...
  4. pmc Ligand induced galectin-3 protein self-association
    Adriana Lepur
    Microbiology, Immunology, and Glycobiology MIG Section, Department of Laboratory Medicine, Lund University, 223 62 Lund, Sweden
    J Biol Chem 287:21751-6. 2012
    ....
  5. pmc The carbohydrate-binding site in galectin-3 is preorganized to recognize a sugarlike framework of oxygens: ultra-high-resolution structures and water dynamics
    Kadhirvel Saraboji
    Department of Biochemistry and Structural Biology, Center for Molecular Protein Science, Box 124, Lund University, SE 221 00 Lund, Sweden
    Biochemistry 51:296-306. 2012
    ..These observations make a case for protein cryo-crystallography as a valuable screening method in fragment-based drug discovery and further suggest that identification of water sites might inform inhibitor design...
  6. ncbi request reprint Protein subtype-targeting through ligand epimerization: talose-selectivity of galectin-4 and galectin-8
    Christopher T Oberg
    Organic Chemistry, Lund University, PO Box 124, SE 221 00 Lund, Sweden
    Bioorg Med Chem Lett 18:3691-4. 2008
    ..Galectin-4C and 8N were found to prefer the d-talopyranose configuration to the natural ligand d-galactopyranose configuration. Derivatization at talose O2 and/or O3 provided selective submillimolar inhibitors for these two galectins...
  7. doi request reprint Monovalent interactions of galectin-1
    Emma Salomonsson
    Institute of Laboratory Medicine, Lund University, Lund, Sweden
    Biochemistry 49:9518-32. 2010
    ..It follows that such weak additional interactions must be important for the biological function of galectin-1 and also for the design of galectin-1 inhibitors...
  8. doi request reprint Arginine binding motifs: design and synthesis of galactose-derived arginine tweezers as galectin-3 inhibitors
    Christopher T Oberg
    Organic Chemistry, Lund University, SE 221 00 Lund, Sweden
    J Med Chem 51:2297-301. 2008
    ..Modeling revealed arginine-144 being pinched by the C3 benzamide and O2 anionic substituents in that the benzamide stacked face-to-face and the anionic O2 substituent ion-paired with the guanidinium moiety...
  9. pmc Galectin-1-binding glycoforms of haptoglobin with altered intracellular trafficking, and increase in metastatic breast cancer patients
    Michael C Carlsson
    Section Microbiology, Immunology, Glycobiology, Department of Laboratory Medicine, Lund University, Lund, Sweden
    PLoS ONE 6:e26560. 2011
    ..In conclusion, galectin-1 detects a new type of functional biomarker for cancer: a specific type of glycoform of haptoglobin, and possibly other serum glycoproteins, with a different function after uptake into tissue cells...
  10. doi request reprint Double affinity amplification of galectin-ligand interactions through arginine-arene interactions: synthetic, thermodynamic, and computational studies with aromatic diamido thiodigalactosides
    Ian Cumpstey
    Organic Chemistry, Lund University, POB 124, 22100 Lund, Sweden
    Chemistry 14:4233-45. 2008
    ..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...
  11. pmc Galectin-3 guides intracellular trafficking of some human serotransferrin glycoforms
    Michael C Carlsson
    From the Section MIG Microbiology, Immunology, Glycobiology, Department of Laboratory Medicine and
    J Biol Chem 288:28398-408. 2013
    ..These are novel aspects of transferrin cell biology, which has previously considered only a degree of iron loading, but not other forms of heterogeneity. ..
  12. doi request reprint Galectin-3 endocytosis by carbohydrate independent and dependent pathways in different macrophage like cell types
    Adriana Lepur
    Section MIG Microbiology, Immunology, Glycobiology, Department of Laboratory Medicine, Lund University, 223 62 Lund, Sweden
    Biochim Biophys Acta 1820:804-18. 2012
    ..We have studied endocytosis of galectin-3 as one important step relevant for its function, and compared it between variants of a macrophage like cell line, and non-macrophage cells...
  13. pmc The anti-angiogenic peptide anginex greatly enhances galectin-1 binding affinity for glycoproteins
    Emma Salomonsson
    Section Microbiology, Immunology, Glycobiology, Institute of Laboratory Medicine, Lund University, Solvegatan 23, SE 223 62 Lund, Sweden
    J Biol Chem 286:13801-4. 2011
    ..Here we show that when bound to anginex, galectin-1 binds various glycoproteins with hundred- to thousand-fold higher affinity. Anginex also interacts with galectin-2, -7, -8N, and -9N but not with galectin-3, -4, or -9C...
  14. ncbi request reprint Galectin-inhibitory thiodigalactoside ester derivatives have antimigratory effects in cultured lung and prostate cancer cells
    Tamara Delaine
    Organic Chemistry, Lund University, POB 124, SE 221 00 Lund, Sweden
    J Med Chem 51:8109-14. 2008
    ..Two of the compounds were selected for testing in cell culture and were shown to have potent antimigratory effects on human PC-3 prostate and human A549 nonsmall-cell lung cancer cells...
  15. doi request reprint Glycoproteomic identification of galectin-3 and -8 ligands in bronchoalveolar lavage of mild asthmatics and healthy subjects
    Cecilia Cederfur
    MIG Microbiology, Immunology, Glycobiology, Dept of Laboratory Medicine Lund, Sweden
    Biochim Biophys Acta 1820:1429-36. 2012
    ..Galectins are found in cells of the airways and in airway secretions, but their glycoprotein ligands there have only been studied to a very limited extent...
  16. pmc Mutational tuning of galectin-3 specificity and biological function
    Emma Salomonsson
    Section MIG, Department of Laboratory Medicine, Lund University, 223 62 Lund, Sweden
    J Biol Chem 285:35079-91. 2010
    ..Finally, the mutants have helped to define the differences in fine specificity shown by Xenopus, mouse, and human galectin-3 and, as such, the evidence for adaptive change during evolution...
  17. doi request reprint Fragment-based development of triazole-substituted O-galactosyl aldoximes with fragment-induced affinity and selectivity for galectin-3
    Johan Tejler
    Organic Chemistry, Lund University, POB 124, SE 22100, Lund, Sweden
    Org Biomol Chem 7:3982-90. 2009
    ..Galectin-7, 8 N-terminal CRD, and 9 N-terminal CRD bound the inhibitors only weakly. The galectin-3 selectivity was hypothesized to stem from interaction of the aldoxime moiety with a site not present in the other galectins...
  18. doi request reprint Different affinity of galectins for human serum glycoproteins: galectin-3 binds many protease inhibitors and acute phase proteins
    Cecilia Cederfur
    Department of Laboratory Medicine, Section MIG Microbiology, Immunology, Glycobiology, Lund University, 223 62 Lund, Sweden
    Glycobiology 18:384-94. 2008
    ....
  19. doi request reprint Arene-anion based arginine-binding motif on a galactose scaffold: structure-activity relationships of interactions with arginine-rich galectins
    Christopher T Oberg
    Organic Chemistry, Lund University, PO Box 124, SE 221 00 Lund, Sweden
    Chemistry 17:8139-44. 2011
    ..In the second series, the electron-donating capacity of the 4-substituent of the C3-benzamides correlated positively with the magnitude of the affinity enhancement by the 2O-sulfate...
  20. ncbi request reprint Synthesis of a 3'-naphthamido-LacNAc fluorescein conjugate with high selectivity and affinity for galectin-3
    Karolina Aplander
    Organic Chemistry, Lund University, P O Box 124, SE 221 00 Lund, Sweden
    Carbohydr Res 341:1363-9. 2006
    ..Its use as a selective and sensitive galectin-3 probe is demonstrated with fluorescence polarization measurements...
  21. ncbi request reprint Synthesis of galactose-mimicking 1H-(1,2,3-triazol-1-yl)-mannosides as selective galectin-3 and 9N inhibitors
    Johan Tejler
    Organic Chemistry, Lund University, PO Box 124, SE 221 00 Lund, Sweden
    Carbohydr Res 342:1869-75. 2007
    ....
  22. ncbi request reprint C2-symmetrical thiodigalactoside bis-benzamido derivatives as high-affinity inhibitors of galectin-3: efficient lectin inhibition through double arginine-arene interactions
    Ian Cumpstey
    Organic Chemistry, Lund University, Box 124, 221 00 Lund, Sweden
    Angew Chem Int Ed Engl 44:5110-2. 2005
  23. pmc Galectin-8 in IgA nephritis: decreased binding of IgA by galectin-8 affinity chromatography and associated increased binding in non-IgA serum glycoproteins
    Michael C Carlsson
    Section MIG Microbiology, Immunology, Glycobiology, Department of Laboratory Medicine, Lund University, Solvegatan 23, 223 62, Lund, Sweden
    J Clin Immunol 32:246-55. 2012
    ..It is caused by accumulation of IgA1-containing immune complexes in the kidney resulting in renal failure, which is thought to be due to altered glycosylation of IgA with a decrease of 2-3-sialylated galactosides (NeuAcα2-3Gal)...
  24. ncbi request reprint Structural and thermodynamic studies on cation-Pi interactions in lectin-ligand complexes: high-affinity galectin-3 inhibitors through fine-tuning of an arginine-arene interaction
    Pernilla Sörme
    Organic and Bioorganic Chemistry, Lund University, P O Box 124, SE 221 00 Lund, Sweden
    J Am Chem Soc 127:1737-43. 2005
    ..The results demonstrate that protein-ligand interactions can be significantly enhanced by the fine-tuning of arginine-arene interactions...
  25. ncbi request reprint 3-(1,2,3-Triazol-1-yl)-1-thio-galactosides as small, efficient, and hydrolytically stable inhibitors of galectin-3
    Bader A Salameh
    Organic Chemistry, Lund University, PO Box 124, SE 221 00 Lund, Sweden
    Bioorg Med Chem Lett 15:3344-6. 2005
    ....
  26. pmc Protein flexibility and conformational entropy in ligand design targeting the carbohydrate recognition domain of galectin-3
    Carl Diehl
    Center for Molecular Protein Science, Biophysical Chemistry, Lund University, P O Box 124, SE 22100 Lund, Sweden
    J Am Chem Soc 132:14577-89. 2010
    ....
  27. ncbi request reprint Studies of arginine-arene interactions through synthesis and evaluation of a series of galectin-binding aromatic lactose esters
    Ian Cumpstey
    Organic Chemistry, Lund University, P O Box 124, Lund, Sweden
    Chembiochem 8:1389-98. 2007
    ..The results provide a basis for the design of lectin inhibitors and drugs that exploit interactions with arginine side-chains via aromatic moieties, which are involved in intramolecular protein salt bridges...
  28. ncbi request reprint Intracellular sorting of galectin-8 based on carbohydrate fine specificity
    Susanne Carlsson
    Institute of Laboratory Medicine, Section of Microbiology Immunology and Glycobiology, Lund University, Solvegatan 23, S 223 62 Lund, Sweden
    Glycobiology 17:906-12. 2007
    ..Moreover, the pattern of galectin-3 after endocytosis differed from that of both the wt and mutant galectin-8. These data clearly demonstrate a role of galectin fine specificity for intracellular targeting...
  29. ncbi request reprint Synthesis of O-galactosyl aldoximes as potent LacNAc-mimetic galectin-3 inhibitors
    Johan Tejler
    Organic Chemistry, Lund University, PO Box 124, SE 221 00 Lund, Sweden
    Bioorg Med Chem Lett 15:2343-5. 2005
    ....
  30. ncbi request reprint Taloside inhibitors of galectin-1 and galectin-3
    Patrick M Collins
    Institute for Glycomics, Gold Coast Campus, Griffith University, Queensland 4222, Australia Organic Chemistry, Lund University, PO Box 124, SE 22100 Lund, Sweden Department of Laboratory Medicine, Lund University, Solvegatan 23, SE 22362 Lund, Sweden
    Chem Biol Drug Des 79:339-46. 2012
    ....
  31. ncbi request reprint Synthesis of multivalent lactose derivatives by 1,3-dipolar cycloadditions: selective galectin-1 inhibition
    Johan Tejler
    Organic Chemistry, Lund University, PO Box 124, SE 221 00 Lund, Sweden
    Carbohydr Res 341:1353-62. 2006
    ..This divalent compound had at least one order of magnitude higher affinity for galectin-1 than for any of the other galectins investigated...
  32. ncbi request reprint Synthesis of a phenyl thio-beta-D-galactopyranoside library from 1,5-difluoro-2,4-dinitrobenzene: discovery of efficient and selective monosaccharide inhibitors of galectin-7
    Ian Cumpstey
    Organic Chemistry, Lund University, Box 124, SE 221 00, Lund, Sweden
    Org Biomol Chem 3:1922-32. 2005
    ..The best inhibitors against galectin-7 were poor against the other galectins and thus have potential as structurally simple and selective tools for dissecting biological functions of galectin-7...
  33. pmc Inhibition mechanism of human galectin-7 by a novel galactose-benzylphosphate inhibitor
    Geoffrey Masuyer
    Department of Biology and Biochemistry, University of Bath, Bath, UK
    FEBS J 279:193-202. 2012
    ..This structural information will allow the design of further inhibitors with improved potency and specificity...
  34. ncbi request reprint Galectin-3 inhibits Schwann cell proliferation in cultured sciatic nerve
    Per Gustavsson
    Department of Cell and Organism Biology, Lund University, Lund, Sweden
    Neuroreport 18:669-73. 2007
    ..We conclude that galectin-3 reduces proliferation of Schwann cells in cultured sciatic nerve segments by a mechanism which is independent of its carbohydrate-binding moiety...
  35. doi request reprint Superantigen- and TLR-dependent activation of tonsillar B cells after receptor-mediated endocytosis
    Johan Jendholm
    Department of Laboratory Medicine, University Hospital Malmo, Lund University, Malmo, Sweden
    J Immunol 182:4713-20. 2009
    ..In conclusion, our findings suggest an important role of TLRs in the adaptive immune response and reveal novel insights into the T cell-independent B cell activation induced by bacteria...
  36. ncbi request reprint Fluorescence polarization as an analytical tool to evaluate galectin-ligand interactions
    Pernilla Sörme
    Organic and Bioorganic Chemistry, Lund University, POB 124, SE 221 00 Lund, Sweden
    Anal Biochem 334:36-47. 2004
    ..As all interaction components are known, K(d) values for galectin-inhibitor interaction can be directly calculated without approximation other than the assumption of a simple one-site competition...
  37. ncbi request reprint Design and synthesis of galectin inhibitors
    Pernilla Sörme
    Department of Bioorganic Chemistry, Lund University, P O Box 124, Lund SE 22100, Sweden
    Methods Enzymol 363:157-69. 2003
  38. ncbi request reprint Efficient and expedient two-step pyranose-retaining fluorescein conjugation of complex reducing oligosaccharides: galectin oligosaccharide specificity studies in a fluorescence polarization assay
    Christopher T Oberg
    Department of Chemistry, University of Waterloo, 200 University Avenue West, Waterloo, Ontario N2L 3G1, Canada
    Bioconjug Chem 14:1289-97. 2003
    ..The results show that fluorescence labeling can be chemically tuned to find optimal probes for individual galectins but also probes interacting well with many galectins...
  39. ncbi request reprint Phylogenetic analysis of the vertebrate galectin family
    Denis Houzelstein
    Laboratoire de Genetique et Developpement des Mammiferes, Institut Jacques Monod, Paris, France
    Mol Biol Evol 21:1177-87. 2004
    ..We show that all vertebrate mono-CRD galectins known to date belong to either the F3- or F4- subtype. A sequence of duplication and divergence events of the different galectins in chordates is proposed...
  40. ncbi request reprint Galectin-4 in normal tissues and cancer
    Margaret E Huflejt
    Sidney Kimmel Cancer Center, 10835 Altman Row, San Diego, CA 92121, USA
    Glycoconj J 20:247-55. 2004
    ..Because of its distinct induction in breast and other cancers, it may be a valuable diagnostic marker and target for the development of inhibitory carbohydrate-based drugs...
  41. pmc Enhancement of bound-state residual dipolar couplings: conformational analysis of lactose bound to Galectin-3
    Tiandi Zhuang
    Complex Carbohydrate Research Center, University of Georgia, Athens, GA 30602, USA
    Protein Sci 15:1780-90. 2006
    ..As an illustration, we have added a propyl chain to the C terminus of the carbohydrate recognition domain of the protein, Galectin-3, and report enhanced RDCs that prove consistent with known bound-ligand geometries for this protein...
  42. ncbi request reprint Affinity of galectin-8 and its carbohydrate recognition domains for ligands in solution and at the cell surface
    Susanne Carlsson
    Section of Microbiology Immunology and Glycobiology MIG, Solvegatan 23, 223 62, Sweden
    Glycobiology 17:663-76. 2007
    ..Also galectin-8 binding and signaling at cell surfaces can be explained by combined binding of the two CRDs to low or medium affinity ligands, and their highest affinity ligands, such as sialylated galactosides, are not required...
  43. ncbi request reprint Complex N-glycans are the major ligands for galectin-1, -3, and -8 on Chinese hamster ovary cells
    Santosh Kumar Patnaik
    Department of Cell Biology, Albert Einstein Collegeof Medicine, New York, NY 10461 USA
    Glycobiology 16:305-17. 2006
    ....