Human galectin-3 selective and high affinity inhibitors. Present state and future perspectives

Current Medicinal Chemistry

Volumn 20, Issue 24, 2013, Pages 2979-2990

  Tellez Sanz R ^a   Garcia Fuentes L ^a   Vargas Berenguel, A ^a  

^a UNIVERSITY OF ALMERÍA   (Spain)

Author keywords

Galectin 3; Inhibitor, selectivity, galactose specific receptor; Lectin

Indexed keywords

AGENTS AFFECTING CARBOHYDRATE METABOLISM; ARGININE; BENZAMIDE DERIVATIVE; BENZENE DERIVATIVE; BETA GALACTOSIDE; ESTER DERIVATIVE; FLUORINE DERIVATIVE; GALECTIN 1; GALECTIN 3; GALECTIN 3 INHIBITOR; GALECTIN 7; GALECTIN 8; UNCLASSIFIED DRUG;

BINDING AFFINITY; BINDING SITE; CANCER INHIBITION; CELL FUNCTION; CHEMICAL STRUCTURE; CONFORMATIONAL TRANSITION; CRYSTAL STRUCTURE; DRUG DESIGN; DRUG SELECTIVITY; DRUG TARGETING; GLYCOLYSIS; HEART FAILURE; HUMAN; HYDROGEN BOND; INHIBITION KINETICS; LIGAND BINDING; NONHUMAN; PROTEIN CARBOHYDRATE INTERACTION; PROTEIN TARGETING; REVIEW; STRUCTURE ACTIVITY RELATION;

ANIMALS; BINDING SITES; GALACTOSIDES; GALECTIN 1; GALECTIN 3; HUMANS; HYDROGEN BONDING; LIGANDS; MODELS, MOLECULAR; PROTEIN BINDING; PROTEIN STRUCTURE, TERTIARY;

EID: 84880262450     PISSN: 09298673     EISSN: 1875533X     Source Type: Journal    
DOI: 10.2174/09298673113209990163     Document Type: Review

References (66)

1. Teichberg, V. I.; Silman, I.; Beitsh, D. D.; Resheff, G. A beta-Dgalactoside binding protein from electric organ tissue of Electrophorus electricus. Proc. Natl. Acad. Sci., 1975, 72, 1383-1387.
2. Barondes, S. H.; Cooper, D. N.; Gitt, M. A.; Leffler, H. Galectins. Structure and function of a large family of animal lectins. J. Biol. Chem., 1994, 269, 20807-20810.
3. Yang, R. Y.; Rabinovich, G. A.; Liu, F. T. Galectins: structure, function and therapeutic potential. Expert Rev. Mol. Med., 2008, 10, e17.
4. Seetharaman, J.; Kanigsberg, A.; Slaaby, R.; Leffler, H.; Barondes, S. H.; Rini, J. M. X-ray crystal structure of the human galectin-3 carbohydrate recognition domain at 2.1-A resolution. J. Biol. Chem., 1998, 273, 13047-13052.
5. Wang, Y.; Nangia-Makker, P.; Tait, L.; Balan, V.; Hogan, V.; Pienta, K. J.; Raz, A. Regulation of prostate cancer progression by galectin-3. Am. J. Pathol., 2009, 174, 1515-1523.
6. Raimond, J.; Zimonjic, D. B.; Mignon, C.; Mattei, M.; Popescu, N. C.; Monsigny, M.; Legrand, A. Mapping of the galectin-3 gene (LGALS3) to human chromosome 14 at region 14q21-22. Mamm. Genome, 1997, 8, 706-707.
7. Bao, Q.; Hughes, R. C. Galectin-3 expression and effects on cyst enlargement and tubulogenesis in kidney epithelial MDCK cells cultured in three-dimensional matrices in vitro. J. Cell Sci., 1995, 108, 2791-2800.
8. Kasper, M.; Hughes, R. C. Immunocytochemical evidence for a modulation of galectin 3 (Mac-2), a carbohydrate binding protein, in pulmonary fibrosis. J. Pathol., 1996, 179, 309-316.
9. Villa-Verde, D. M.; Silva-Monteiro, E.; Jasiulionis, M. G.; Farias-De-Oliveira, D. A.; Brentani, R. R.; Savino, W.; Chammas, R. Galectin-3 modulates carbohydrate-dependent thymocyte interactions with the thymic microenvironment. Eur. J. Immunol., 2002, 32, 1434-1444.
10. Shekhar, M. P.; Nangia-Makker, P.; Tait, L.; Miller, F.; Raz, A. Alterations in galectin-3 expression and distribution correlate with breast cancer progression: functional analysis of galectin-3 in breast epithelial-endothelial interactions. Am. J. Pathol., 2004, 165, 1931-1941.
11. Hrdlickova-Cela, E.; Plzak, J.; Smetana, K., Jr.; Melkova, Z.; Kaltner, H.; Filipec, M.; Liu, F. T.; Gabius, H. J. Detection of galectin-3 in tear fluid at disease states and immunohistochemical and lectin histochemical analysis in human corneal and conjunctival epithelium. Br. J. Ophthalmol., 2001, 85, 1336-1340.
12. Teymoortash, A.; Pientka, A.; Schrader, C.; Tiemann, M.; Werner, J. A. Expression of galectin-3 in adenoid cystic carcinoma of the head and neck and its relationship with distant metastasis. J. Cancer Res. Clin. Oncol., 2006, 132, 51-56.
13. Schaffert, C.; Pour, P. M.; Chaney, W. G. Localization of galectin-3 in normal and diseased pancreatic tissue. Int. J. Pancreatol., 1998, 23, 1-9.
14. Okada, K.; Shimura, T.; Suehiro, T.; Mochiki, E.; Kuwano, H. Reduced galectin-3 expression is an indicator of unfavorable prognosis in gastric cancer. Anticancer Res., 2006, 26, 1369-1376.
15. Tsuboi, K.; Shimura, T.; Masuda, N.; Ide, M.; Tsutsumi, S.; Yamaguchi, S.; Asao, T.; Kuwano, H. Galectin-3 expression in colorectal cancer: relation to invasion and metastasis. Anticancer Res., 2007, 27, 2289-2296.
16. Shimonishi, T.; Miyazaki, K.; Kono, N.; Sabit, H.; Tuneyama, K.; Harada, K.; Hirabayashi, J.; Kasai, K.; Nakanuma, Y. Expression of endogenous galectin-1 and galectin-3 in intrahepatic cholangiocarcinoma. Hum. Pathol., 2001, 32, 302-310.
17. Stock, M.; Schafer, H.; Stricker, S.; Gross, G.; Mundlos, S.; Otto, F. Expression of galectin-3 in skeletal tissues is controlled by Runx2. J. Biol. Chem., 2003, 278, 17360-17367.
18. Niida, S.; Amizuka, N.; Hara, F.; Ozawa, H.; Kodama, H. Expression of Mac-2 antigen in the preosteoclast and osteoclast identified in the op/op mouse injected with macrophage colony-stimulating factor. J. Bone Miner. Res., 1994, 9, 873-881.
19. Wollenberg, A.; de la Salle, H.; Hanau, D.; Liu, F. T.; Bieber, T. Human keratinocytes release the endogenous beta-galactosidebinding soluble lectin immunoglobulin E (IgE-binding protein) which binds to Langerhans cells where it modulates their binding capacity for IgE glycoforms. J. Exp. Med., 1993, 178, 777-785.
20. Reichert, F.; Saada, A.; Rotshenker, S. Peripheral nerve injury induces Schwann cells to express two macrophage phenotypes: phagocytosis and the galactose-specific lectin MAC-2. J. Neurosci., 1994, 14, 3231-3245.
21. Lotan, R.; Belloni, P. N.; Tressler, R. J.; Lotan, D.; Xu, X. C.; Nicolson, G. L. Expression of galectins on microvessel endothelial cells and their involvement in tumor cell adhesion. Glycoconj. J., 1994, 11, 462-468.
22. Barboni, E. A.; Bawumia, S.; Henrick, K.; Hughes, R. C. Molecular modeling and mutagenesis studies of the N-terminal domains of galectin-3: evidence for participation with the C-terminal carbohydrate recognition domain in oligosaccharide binding. Glycobiology, 2000, 10, 1201-1208.
23. Ochieng, J.; Furtak, V.; Lukyanov, P. Extracellular functions of galectin-3. Glycoconj. J., 2004, 19, 527-535.
24. Liu, F. T.; Patterson, R. J.; Wang, J. L. Intracellular functions of galectins. Biochim. Biophys. Acta, 2002, 1572, 263-273.
25. Balan, V.; Nangia-Makker, P.; Raz, A. Galectins as cancer biomarkers. Cancers, 2010, 2, 592-610.
26. St-Pierre, Y. Galectins in hematological malignancies. Am. J. Blood Res., 2011, 1, 119-129.
27. Vasta, G. R. Roles of galectins in infection. Nat. Rev.Microbiol., 2009, 7, 424-438.
28. Dhirapong, A.; Lleo, A.; Leung, P.; Gershwin, M. E.; Liu, F. T. The immunological potential of galectin-1 and -3. Autoimmun. Rev., 2009, 8, 360-363.
29. Liu, F. T. Regulatory roles of galectins in the immune response. Int. Arch. Allergy Immunol., 2005, 136, 385-400.
30. Nangia-Makker, P.; Balan, V.; Raz, A. Regulation of tumor progression by extracellular galectin-3. Cancer Microenviron., 2008, 1, 43-51.
31. Caberoy, N. B.; Alvarado, G.; Bigcas, J. L.; Li, W. Galectin-3 is a new MerTK-specific eat-me signal. J. Cell. Physiol., 2012, 227, 401-407.
32. Oliveira, F. L; Brand, C.; Paula, A. A.; Arcanjo, K. D.; Hsu, D. K.; Liu, F. T.; Takiya, C. M.; Borojevic, R.; Chammas, R.; El-Cheikh, M. C. Lack of galectin-3 disturbs mesenteric lymph node homeostasis and B cell niches in the course of Schistosoma mansoni infection. PLoS One, 2011, 6, e19216.
33. Strik, H.M.; Kolodziej. M.; Oertel, W.; Basecke, J. Glycobiology in malignant gliomas: expression and functions of galectins and possible therapeutic options. Curr. Pharm. Biotechnol., 2012, 13, 2299-2307.
34. McCullough, P. A.; Olobatoke, A.; Vanhecke, T. E. Galectin-3: a novel blood test for the evaluation and management of patients with heart failure. Rev. Cardiovasc. Med., 2011, 12, 200-210.
35. deFilippi, C. R.; Felker, G. M. Galectin-3 in heart failure -Linking fibrosis, remodeling and progression. European Cardiology, 2010, 6, 33-36.
36. Kramer, F. Galectin-3: clinical utility and prognostic value in patients with heart failure. Res. Rep. Clin. Cardiol., 2013, 4, 13-22.
37. Traber, P. G.; Chou, H.; Zomer, E.; Hong, F.; Klyosov, A.; Fiel, M.-I.; Friedman, S.L. Regression of fibrosis and reversal of cirrhosis in thioacetamide-induced liver fibrosis following treatment with galectin inhibitors. J. Hepatol., 2013, 58, S462-S463.
38. Leffler, H.; Carlsson, S.; Hedlund, M.; Qian, Y.; Poirier, F. Introduction to galectins. Glycoconj. J., 2004, 19, 433-440.
39. Ahmad, N.; Gabius, H. J.; Sabesan, S.; Oscarson, S.; Brewer, C. F. Thermodynamic binding studies of bivalent oligosaccharides to galectin-1, galectin-3, and the carbohydrate recognition domain of galectin-3. Glycobiology, 2004, 14, 817-825.
40. Vrasidas, I.; Andre, S.; Valentini, P.; Bock, C.; Lensch, M.; Kaltner, H.; Liskamp, R. M.; Gabius, H. J.; Pieters, R. J. Rigidified multivalent lactose molecules and their interactions with mammalian galectins: a route to selective inhibitors. Org. Biomol. Chem., 2003, 1, 803-810.
41. Cumpstey, I.; Carlsson, S.; Leffler, H.; Nilsson, U. J. 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. Org. Biomol. Chem., 2005, 3, 1922-1932.
42. Dam, T. K.; Gabius, H. J.; Andre, S.; Kaltner, H.; Lensch, M.; Brewer, C. F. Galectins bind to the multivalent glycoprotein asialofetuin with enhanced affinities and a gradient of decreasing binding constants. Biochemistry, 2005, 44, 12564-12571.
43. Giguere, D.; Patnam, R.; Bellefleur, M. A.; St-Pierre, C.; Sato, S.; Roy, R. Carbohydrate triazoles and isoxazoles as inhibitors of galectins-1 and -3. Chem. Commun., 2006, 22, 2379-2381.
44. Rabinovich, G. A.; Cumashi, A.; Bianco, G. A.; Ciavardelli, D.; Iurisci, I.; D'Egidio, M.; Piccolo, E.; Tinari, N.; Nifantiev, N.; Iacobelli, S. Synthetic lactulose amines: novel class of anticancer agents that induce tumor-cell apoptosis and inhibit galectinmediated homotypic cell aggregation and endothelial cell morphogenesis. Glycobiology, 2006, 16, 210-220.
45. Cederfur, C.; Salomonsson, E.; Nilsson, J.; Halim, A.; Oberg, C. T.; Larson, G.; Nilsson, U. J.; Leffle, H. Different affinity of galectins for human serum glycoproteins: Galectin-3 binds many protease inhibitors and acute phase proteins. Glycobiology, 2008, 18, 384-394.
46. Oberg, C. T.; Blanchard, H.; Leffler, H.; Nilsson, U. J. Protein subtype-targeting through ligand epimerization: talose-selectivity of galectin-4 and galectin-8. Bioorg. Med. Chem. Lett., 2008, 18, 3691-3694.
47. Delaine, T.; Cumpstey, I.; Ingrassia, L.; Le Mercier, M.; Okechukwu, P.; Leffler, H.; Kiss, R.; Nilsson, U. J. Galectin-inhibitory thiodigalactoside ester derivatives have antimigratory effects in cultured lung and prostate cancer cells. J. Med. Chem., 2008, 51, 8109-8114.
48. Giguere, D.; Bonin, M. A.; Cloutier, P.; Patnam, R.; St-Pierre, C.; Sato, S.; Roy, R. Synthesis of stable and selective inhibitors of human galectins-1 and -3. Bioorg. Med. Chem., 2008, 16, 7811-7823.
49. Tejler, J.; Salameh, B.; Leffler, H.; Nilsson, U. J. Fragment-based development of triazole-substituted O-galactosyl aldoximes with fragment-induced affinity and selectivity for galectin-3. Org. Biomol. Chem., 2009, 7, 3982-3990.
50. Iurisci, I.; Cumashi, A.; Sherman, A. A.; Tsvetkov, Y. E.; Tinari, N.; Piccolo, E.; D'Egidio, M.; Adamo, V.; Natoli, C.; Rabinovich, G. A.; Iacobelli, S.; Nifantiev, N. E. Synthetic inhibitors of galectin-1 and -3 selectively modulate homotypic cell aggregation and tumor cell apoptosis. Anticancer Res., 2009, 29, 403-410.
51. Saraboji, K.; Hakansson, M.; Genheden, S.; Diehl, C.; Qvist, J.; Weininger, U.; Nilsson, U. J.; Leffler, H.; Ryde, U.; Akke, M.; Logan, D. T. The carbohydrate-binding site in galectin-3 is preorganized to recognize a sugarlike framework of oxygens: ultra-highresolution structures and water dynamics. Biochemistry, 2012, 51, 296-306.
52. Umemoto, K.; Leffler, H.; Venot, A.; Valafar, H.; Prestegard, J. H. Conformational differences in liganded and unliganded states of Galectin-3. Biochemistry, 2003, 42, 3688-36895.
53. Sorme, P.; Arnoux, P.; Kahl-Knutsson, B.; Leffler, H.; Rini, J. M.; Nilsson, U. J. 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. J. Am. Chem. Soc., 2005, 127, 1737-1743.
54. Cumpstey, I.; Sundin, A.; Leffler, H.; Nilsson, U. J. C2-symmetrical thiodigalactoside bis-benzamido derivatives as highaffinity inhibitors of Galectin-3: efficient lectin inhibition through double arginine-Arene interactions. Angew. Chem. Int. Ed., 2005, 44, 5110-5112.
55. Oberg, C. T.; Leffler, H.; Nilsson, U. J. Arginine binding motifs: design and synthesis of galactose-derived arginine tweezers as galectin-3 inhibitors. J. Med. Chem., 2008, 51, 2297-2301.
56. Cumpstey, I.; Salomonsson, E.; Sundin, A.; Leffler, H.; Nilsson, U. J. Double affinity amplification of galectin-ligand interactions through arginine-Arene interactions: synthetic, thermodynamic, and computational studies with aromatic diamido thiodigalactosides. Chem. Eur. J., 2008, 14, 4233-4245.
57. Reina, J.J.; Bernardi, A. Carbohydrate mimics and lectins: a source of new drugs and therapeutic opportunities. Mini Rev. Med. Chem., 2012, 12, 1434-1442.
58. Badji, J. D.; Nelson, A.; Cantrill, S. J.; Turnbull, W. B.; Stoddart, J. F. Multivalency and cooperativity in supramolecular chemistry. Acc. Chem. Res., 2005, 38, 723-732.
59. Van Scherpenzeel, M.; Moret, E. E.; Ballell, L.; Liskamp, R. M. J.; Nilsson, U. J.; Leffler, H.; Pieters, R. J. Synthesis and evaluation of new thiodigalactoside-based chemical probes to label galectin-3. ChemBioChem, 2009, 10, 1724-1733.
60. Patnaik, S. K.; Potvin, B.; Carlsson, S.; Sturm, D.; Leffler, H.; Stanley, P. Complex N-glycans are the major ligands for galectin-1, -3, and -8 on Chinese hamster ovary cells. Glycobiology, 2006, 16, 305-317.
61. Andre, S.; Maljaars, C. E.; Halkes, K. M.; Gabius, H. J.; Kamerling, J. P. Discovery of galectin ligands in fully randomized combinatorial one-bead-one-compound (glyco)peptide libraries. Bioorg. Med. Chem. Lett., 2007, 17, 793-798.
62. Zou, J.; Glinsky, V. V.; Landon, L. A.; Matthews, L.; Deutscher, S. L. Peptides specific to the galectin-3 carbohydrate recognition domain inhibit metastasis-Associated cancer cell adhesion. Carcinogenesis, 2005, 26, 309-318.
63. Newton-Northup, J. R.; Dickerson, M. T.; Ma, L.; Besch-Williford, C. L.; Deutscher, S. L. Inhibition of metastatic tumor formation in vivo by a bacteriophage display-derived galectin-3 targeting peptide. Clin. Exp. Metastasis, 2013, 30, 119-132.
64. Cumpstey, I.; Salomonsson, E.; Sundin, A.; Leffler, H.; Nilsson, U. J. Studies of arginine-Arene interactions through synthesis and evaluation of a series of galectin-binding aromatic lactose esters. ChemBioChem, 2007, 8, 1389-1398.
65. Collins, P. M.; Oberg, C. T.; Leffler, H.; Nilsson, U. J.; Blanchard, H. Taloside inhibitors of galectin-1 and galectin-3. Chem. Biol. Drug. Des., 2012, 79, 339-346.
66. Diehl, C.; Engstrom, O.; Delaine, T.; Hakansson, M.; Genheden, S.; Modig, K.; Leffler, H.; Ryde, U.; Nilsson, U. J.; Akke, M. Protein flexibility and conformational entropy in ligand design targeting the carbohydrate recognition domain of galectin-3. J. Am. Chem. Soc., 2010, 132, 14577-14589.