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Review

Galectin-1 inhibitors and their potential therapeutic applications: a patent review

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Pages 537-554 | Received 06 Sep 2015, Accepted 04 Mar 2016, Published online: 25 Mar 2016

References

  • Barondes SH, Cooper DN, Gitt MA, et al. Galectins. Structure and function of a large family of animal lectins. J Biol Chem. 1994;269:20807–20810.
  • Leffler H, Carlsson S, Hedlund M, et al. Introduction to galectins. Glycoconj J. 2004;19:433–440.
  • Sacchettini JC, Baum LG, Brewer CF. Multivalent protein-carbohydrate interactions. A new paradigm for supermolecular assembly and signal transduction. Biochemistry. 2001;40:3009–3015.
  • Fred Brewer C. Binding and cross-linking properties of galectins. Biochim Biophys Acta. 2002;1572:255–262.
  • Hirabayashi J, Hashidate T, Arata Y, et al. Oligosaccharide specificity of galectins: a search by frontal affinity chromatography. Biochim Biophys Acta. 2002;1572:232–254.
  • Camby I, Le Mercier M, Lefranc F, et al. Galectin-1: a small protein with major functions. Glycobiology. 2006;16:137R–57R.
  • Liu FT, Patterson RJ, Wang JL. Intracellular functions of galectins. Biochim Biophys Acta. 2002;1572:263–273.
  • Patterson RJ, Wang W, Wang JL. Understanding the biochemical activities of galectin-1 and galectin-3 in the nucleus. Glycoconj J. 2004;19:499–506.
  • He J, Baum LG. Galectin interactions with extracellular matrix and effects on cellular function. Methods Enzymol. 2006;417:247–256.
  • Puche AC, Poirier F, Hair M, et al. Role of galectin-1 in the developing mouse olfactory system. Dev Biol. 1996;179:274–287.
  • Wada M, Ono S, Kadoya T, et al. Decreased galectin-1 immunoreactivity of the skin in amyo- trophic lateral sclerosis. J Neurol Sci. 2003;208:67–70.
  • Wang J, Xia J, Zhang F, et al. Galectin-1-secreting neural stem cells elicit long-term neuroprotection against ischemic brain injury. Sci Rep. 2015;5:9621.
  • Hughes RC. Secretion of the galectin family of mammalian carbohydrate-binding proteins. Biochim Biophys Acta. 1999;1473:172–185.
  • Cooper DN, Barondes SH. Evidence for export of a muscle lectin from cytosol to extracellular matrix and for a novel secretory mechanism. J Cell Biol. 1990;110:1681–1691.
  • Cho M, Cummings RD. Galectin-1, a beta-galactoside-binding lectin in Chinese hamster ovary cells. I. Physical and chemical characterization. J Biol Chem. 1995;270:5198–5206.
  • Vasta GR. Galectins as pattern recognition receptors: structure, function, and evolution. Adv Exp Med Biol. 2012;946:21–36.
  • Ito K, Stannard K, Gabutero E, et al. Galectin-1 as a potent target for cancer therapy: role in the tumor microenvironment. Cancer Metastasis Rev. 2012;31:763–778.
  • Demydenko D, Berest I. Expression of galectin-1 in malignant tumors. Exp Oncol. 2009;31:74–79.
  • Braeuer RR, Shoshan E, Kamiya T, et al. The sweet and bitter sides of galectins in melanoma progression. Pigment Cell Melanoma Res. 2012;25:592–601.
  • Barrow H, Rhodes JM, Yu LG. The role of galectins in colorectal cancer progression. Int J Cancer. 2011;129:1–8.
  • Verschuere T, De Vleeschouwer S, Lefranc F, et al. Galectin-1 and immunotherapy for brain cancer. Expert Rev Neurother. 2011;11:533–543.
  • Smetana K Jr, Szabo P, Gal P, et al. Emerging role of tissue lectins as microenvironmental effectors in tumors and wounds. Histol Histopathol. 2015;30:293–309.
  • Berois N, Osinaga E. Glycobiology of neuroblastoma: impact on tumor behavior, prognosis, and therapeutic strategies. Front Oncol. 2014;4:114–127.
  • Bacigalupo ML, Manzi M, Rabinovich GA, et al. Hierarchical and selective roles of galectins in hepatocarcinogenesis, liver fibrosis and inflammation of hepatocellular carcinoma. World J Gastroenterol. 2013;19:8831–8849.
  • Thijssen VL, Heusschen R, Caers J, et al. Galectin expression in cancer diagnosis and prognosis: a systematic review. Biochim Biophys Acta. 2015;1855:235–247.
  • Thijssen VLJL, Postel R, Brandwijk RJ, et al. Galectin-1 is essential in tumor angiogenesis and is a target for antiangiogenesis therapy. Proc Natl Acad Sci. 2006;103:15975–15980.
  • Thijssen VL, Griffioen AW. Galectin-1 and -9 in angiogenesis: a sweet couple. Glycobiology. 2014;24:915–920.
  • Croci DO, Cerliani JP, Pinto NA, et al. Regulatory role of glycans in the control of hypoxia-driven angiogenesis and sensitivity to anti-angiogenic treatment. Glycobiology. 2014;24:1283–1290.
  • Sakaguchi M, Okano H. Neural stem cells, adult neurogenesis, and galectin-1: from bench to bedside. Dev Neurobiol. 2012;72:1059–1067.
  • Rabinovich GA. Galectin-1 as a potential cancer target. Br J Cancer. 2005;92:1188–1192.
  • Astorgues-Xerri L, Riveiro ME, Tijeras-Raballand A, et al. Unraveling galectin-1 as a novel therapeutic target for cancer. Cancer Treat Rev. 2014;40:307–319.
  • Strik HM, Kolodziej M, Oertel W, et al. Glycobiology in malignant gliomas: expression and functions of galectins and possible therapeutic options. Curr Pharm Biotechnol. 2012;13:2299–2307.
  • Messaoudi K, Clavreul A, Lagarce F. Toward an effective strategy in glioblastoma treatment. Part I: resistance mechanisms and strategies to overcome resistance of glioblastoma to temozolomide. Drug Discov Today. 2015;20:899–907.
  • Mercier S, St-Pierre C, Pelletier I, et al. Galectin-1 promotes HIV-1 infectivity in macrophages through stabilization of viral adsorption. Virology. 2008;371:121–129.
  • St-Pierre C, Manya H, Ouellet M, et al. Host-soluble galectin-1 promotes HIV-1 replication through a direct interaction with glycans of viral gp120 and host CD4. J Virol. 2011;85:11742–11751.
  • St-Pierre C, Ouellet M, Giguere D, et al. Galectin-1-specific inhibitors as a new class of compounds to treat HIV-1 infection. Antimicrob Agents Chemother. 2012;56:154–162.
  • Perillo NL, Pace KE, Seilhamer JJ, et al. Apoptosis of T cells mediated by galectin-1. Nature. 1995;378:736–739.
  • Toscano MA, Bianco GA, Ilarregui JM, et al. Differential glycosylation of TH1, TH2 and TH-17 effector cells selectively regulates susceptibility to cell death. Nat Immunol. 2007;8:825–834.
  • Blaser C, Kauffmann M, Muller C, et al. β-galactoside-binding protein secreted by activated T cells inhibits antigen-induced proliferation of T cells. Eur J Immunol. 1998;28:2311–2319.
  • Rabinovich GA, Modesti NM, Castagna LF, et al. Specific inhibition of lymphocyte proliferation and induction of apoptosis by CLL-I, a β-galactoside-binding lectin. J Biochem. 1997;122:365–373.
  • Rabinovich GA, Daly G, Dreja H, et al. Recombinant 
galectin-1 and its genetic delivery suppress collagen-induced arthritis via T-cell apoptosis. J Exp Med. 1999;190:385–398.
  • Santucci L, Fiorucci S, Cammilleri F, et al. Galectin-1 exerts immunomodulatory and protective effects on concanavalin-A-induced hepatitis in mice. Hepatology. 2000;31:399–406.
  • Hsu DK, Yang RY, Pan Z, et al. Targeted disruption of the galectin-3 gene results in attenuated peritoneal inflammatory responses. Am J Pathol. 2000;156:1073–1083.
  • Cortegano I, Del Pozo V, Cardaba B, et al. Galectin-3 down- regulates IL-5 gene expression on different cell types. J Immunol. 1998;161:385–389.
  • Karlsson A, Follin P, Leffler H, et al. Galectin-3 activates the NADPH oxidase in exudated but not peripheral-blood neutrophils. Blood. 1998;91:3430–3438.
  • Rabinovich GA, Baum LG, Tinari N, et al. Galectins and their ligands: amplifiers, silencers or tuners of the inflammatory response? Trends Immunol. 2002;23:313–320.
  • Almkvist J, Karlsson A. Galectins as inflammatory mediators. Glycoconj J. 2004;19:575–581.
  • Mizoguchi E, Mizoguchi A. Is the sugar always sweet in intestinal inflammation? Immunol Res. 2007;37:47–60.
  • Liu FT. Galectins: novel anti-inflammatory drug targets. Expert Opin Ther Targets. 2002;6:461–468.
  • Cedeno-Laurent F, Dimitroff CJ. Galectin-1 research in T cell immunity: past, present and future. Clin Immunol. 2012;142:107–116.
  • Salatino M, Croci DO, Bianco GA, et al. Galectin-1 as a potential therapeutic target in autoimmune disorders and cancer. Expert Opin Biol Ther. 2008;8:45–57.
  • Hokama A, Mizoguchi E, Mizoguchi A. Roles of galectins in inflammatory bowel disease. World J Gastroenterol. 2008;14:5133–5137.
  • La M, Cao TV, Cerchiaro G, et al. A novel biological activity for galectin-1: inhibition of leukocyte-endothelial cell interactions in experimental inflammation. Am J Pathol. 2003;163:1505–1515.
  • Cooper D, Norling LV, Perretti M. Novel insights into the inhibitory effects of Galectin-1 on neutrophil recruitment under flow. J Leukoc Biol. 2008 Jun;83:1459–1466.
  • Rabinovich GA, Sotomayor CE, Riera CM, et al. Evidence of a role for galectin-1 in acute inflammation. Eur J Immunol. 2000;30:1331–1339.
  • Smetana K Jr, André S, Kaltner H, et al. Context-dependent multifunctionality of galectin-1: a challenge for defining the lectin as therapeutic target. Expert Opin Ther Targets. 2013;17:379–392.
  • Lopez-Lucendo MF, Solis D, Andre S, et al. Growth-regulatory human galectin-1: crystallographic characterisation of the structural changes induced by single-site mutations and their impact on the thermodynamics of ligand binding. J Mol Biol. 2004;343:957–970.
  • Salomonsson E, Larumbe A, Tejler J, et al. Monovalent interactions of galectin-1. Biochemistry. 2010;49:9518–9532.
  • Leppanen A, Stowell S, Blixt O, et al. Dimeric galectin-1 binds with high affinity to alpha2,3-sialylated and non-sialylated terminal N-acetyllactosamine units on surface-bound extended glycans. J Biol Chem. 2005;280:5549–5562.
  • Cho M, Cummings RD. Characterization of monomeric forms of galectin-1 generated by site-directed mutagenesis. Biochemistry. 1996;35:13081–13088.
  • Kasai K-I, Hirabayashi J. Galectins: a family of animal lectins that decipher glycocodes. J Biochem. 1996;119:1–8.
  • Kadoya T, Horie H. Structural and functional studies of galectin-1: a novel axonal regeneration-promoting activity for oxidized galectin-1. Curr Drug Targets. 2005;6:375–383.
  • Pande AH, Gupta RK, Sumati, et al. Oxidation of goat hepatic galectin-1 induces change in secondary structure. Protein Pept Lett. 2003;10:265–275.
  • Hirabayashi J, Kasai K. Effect of amino acid substitution by sited-directed mutagenesis on the carbohydrate recognition and stability of human 14-kDa beta-galactoside-binding lectin. J Biol Chem. 1991;266:23648–23653.
  • Abbott WM, Feizi T. Soluble 14-kDa beta-galactoside-specific bovine lectin. Evidence from mutagenesis and proteolysis that almost the complete polypeptide chain is necessary for integrity of the carbohydrate recognition domain. J Biol Chem. 1991;266:5552–5557.
  • Nishi N, Abe A, Iwaki J, et al. Functional and structural bases of a cysteine-less mutant as a long-lasting substitute for galectin-1. Glycobiology. 2008;18:1065–1073.
  • Guardia CM, Caramelo JJ, Trujillo M, et al. Structural basis of redox-dependent modulation of galectin-1 dynamics and function. Glycobiology. 2014;24:428–441.
  • Horie H, Kadoya T, Hikawa N, et al. Oxidized galectin-1 stimulates macrophages to promote axonal regeneration in peripheral nerves after axotomy. J Neurosci. 2004;24:1873–1880.
  • Paz A, Haklai R, Elad-Sfadia G, et al. Galectin-1 binds oncogenic H-Ras to mediate Ras membrane anchorage and cell transformation. Oncogene. 2001;20:7486–7493.
  • Elad-Sfadia G, Haklai R, Ballan E, et al. Galectin-1 augments Ras activation and diverts Ras signals to Raf-1 at the expense of phosphoinositide 3-kinase. J Biol Chem. 2002;277:37169–37175.
  • Yu X, Scott SA, Pritchard R, et al. Redox state influence on human galectin-1 function. Biochimie. 2015;116:8–16.
  • Rotblat B, Niv H, Andre S, et al. Galectin-1(L11A) predicted from a computed galectin-1 farnesyl-binding pocket selectively inhibits Ras-GTP. Cancer Res. 2004;64:3112–3118.
  • Tejler J, Salameh B, Leffler H, et al. Fragment-based development of triazole-substituted O-galactosyl aldoximes with fragment-induced affinity and selectivity for galectin-3. Org Biomol Chem. 2009;7:3982.
  • Van Hattum H, Branderhorst HM, Moret EE, et al. Tuning the preference of thiodigalactoside- and lactosamine-based ligands to galectin-3 over galectin-1. J Med Chem. 2013;56:1350–1354.
  • Cumpstey I, Carlsson S, Leffler H, et al. 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.
  • Giguère D, Patnam R, Bellefleur M, et al. Carbohydrate triazoles and isoxazoles as inhibitors of galectins-1 and -3. Chem Commun (Camb). 2006;22:2379–2381.
  • Giguère D, Sato S, St-Pierre C, et al. Aryl O- and S-galactosides and lactosides as specific inhibitors of human galectins-1 and -3: role of electrostatic potential at O-3. Bioorg Med Chem Lett. 2006;16:1668–1672.
  • Giguere D, Bonin MA, Cloutier P, et al. Synthesis of stable and selective inhibitors of human galectins-1 and -3. Bioorg Med Chem. 2008;16:7811–7823.
  • Pandey RK, Dougherty TJ. Galectin recognized photosensitizers for photodynamic therapy. US6849607B2 2005.
  • Huflejt M, Mossine V, Croft M. Galectins -1 and -4 in tumor development. US20030109464A1 2003.
  • Ralph SJ Immunomodulating compositions and uses thereof. US9050352B2 2015.
  • Leffler H, Salameh B, Nilsson U. 3-Triazolyl-galactoside inhibitors of galectins. US7700763B2 2010.
  • Nilsson U, Leffler H, Mukhopadhyay B, et al. Novel galectoside inhibitors of galectins. US20140336146A1 2014.
  • Nilsson U, Leffler H, Henderson N, et al. Galactoside inhibitor of galectin-3 and its use for treating pulmonary fibrosis. WO2014067986A1 2014.
  • Klyosov A, Platt D Co-administration of a polysaccharide with a chemotherapeutic agent for the treatment of cancer. US7012068B2 2006.
  • Platt D, Klyosov A Selectively depolymerized galactomannan polysaccharide. US7893252B2 2011.
  • Platt D, Zomer E, Klyosov A Galactose-pronged polysaccharides in a formulation for antifibrotic therapies. US8722645B2 2014.
  • Traber PG, Zomer E, Klyosov AA. Galacto-rhamnogalacturonate compositions for the treatment of non-alcoholic steatohepatitis and non-alcoholic fatty liver disease. US8658787B2 2014.
  • Zomer E, Traber PG, Klyosov AA, et al. Composition of novel carbohydrate drug for treatment of human diseases. US8962824B2 2015.
  • Traber PG. Method for treatment of pulmonary fibrosis. US20140235571A1 2014.
  • Traber PG, Redmond WL, Zomer E, et al. Method for enhancing specific immunotherapies in cancer treatment. US20140086932A1 2014.
  • Traber PG, Zomer E, Klyosov AA. Galacto-rhamnogalacturonate compositions for the treatment of diseases associated with elevated inducible nitric oxide synthase. US20150147338A1 2015.
  • Staples M, Rolke J Modified pectins, compositions and methods related thereto. US8877263B2 2014.
  • Chang Y, Sasak V Composition and uses of galectin antagonist. US2015133399A1 2015.
  • Chang Y, Sasak V Method and material for treating immune diseases. US20030004132A1 2003.
  • Chang Y, Sasak V Method for controlling angiogenesis in animals. US20040121981A1 2004.
  • Chang Y Method for treating neurodegenerative diseases. US20060014719A1 2006.
  • Chang Y, Cotter F Composition and method for treating hyperproliferative diseases. US20060074050A1 2006.
  • Mayo K, Dings R, Griffin R Tumor treatment using beta-sheet peptides and radiotherapy. US2007010438A1 2007.
  • Glcogenesys Inc. Functionally active recombinant peptides, methods for producing same and interactions with other peptides. WO2006128027A1 2006.
  • Mayo KH, Hoye TR, Flader-Lavey C Partial peptide mimetics and methods. US7339023B2 2008.
  • Mayo KH, Hoye TR, Chen X Calixarene-based peptide conformation mimetics, methods of use, and methods of making. US8716343B2 2014.
  • Astorgues-Xerri L, Cvitkovic E, Faivre S, et al. Compounds inhibiting galectin-1 expression, cancer cell proliferation, invasion, and tumorigenesis. WO2012131079A1 2012.
  • Mayo KH Anti-tumor agent otx-008 targets human galectin-1. WO2014070214A1 2014.
  • Läppchen T, Gruell H, Robillard MS, et al. Analog (s) radiolabeled (s) of a 0118 and its/their use in connection with PET imaging and/or compound spect to determine if a pharmaceutical product containing the compound 0118 is a candidate anti-cancer treatment for a patient. EP2858681 2015.
  • Dings RP, Hoye TR, Levine JI, et al. Cytotoxic agents against cancer cells and uses thereof. WO2012061395A2 2012.
  • Saraiva MJ, Vanlandschoot P, Dolk E, et al. Amino acid sequences directed against multitarget scavenger receptors and polypeptides. US9034325B2 2015.
  • Shipp MA, Ouyang J, Rodig SJ Anti-galectin-1 (gal1) monoclonal antibodies and fragments thereof for neutralizing gal1. WO2015013388A2 2015.
  • Shipp MA, Ouyang J, Takeyama K, et al. Compositions, kits, and methods for the diagnosis, prognosis, monitoring, treatment and modulation of post-transplant lymphoproliferative disorders and hypoxia associated angiogenesis disorders using galectin-1. US8968740B2 2015.
  • Okano H, Sawamoto K, Sakaguchi M, et al. Agent for inhibiting proliferation of neural stem cells. US7662385B2 2010.
  • Camby I, Henriet P, Lefranc F, et al. Use of a galectin-1-targeted RNAi-based approach for the treatment of cancer. US7964575B2 2011.
  • Payne RM, Babbey CM, Martin KB, et al. Gigaxonin fusion protein and methods for treating giant axonal neuropathy. EP2771367 2014.
  • Dartt D Methods and compositions for modulating conjunctival goblet cells. US20070185014A1 2007.
  • Panjwani N. Composition and uses of a galectin for treatment of dry eye syndrome. US20100004163A1 2010.
  • Jun W Preventives/remedies for nephritis. WO2002089831A1 2002.
  • Cummings RD, Cho MJ. Methods of screening for compounds which mimic galectin-1. US5948628A 1999.
  • Cummings RD, Cho MJ. Methods of screening for compounds which mimic galectin-1. US6225071B1 2001.
  • Dimitroff CJ, Laurent FC, Barthel SR Galectin-immunoglobulin chimeric molecules. US8598323B2 2013.
  • Horie H, Inagaki Y, Sohma Y, et al. Neuronal growth factor galectin-1. US6890531B1 2005.
  • John C, Unger G Biologic modulations with nanoparticles. US20040023855A1 2004.
  • Chao-Liang W, Yen-Jang H, Ai-Li S, et al. Galectin-1-gold particle complex and applications thereof. TW201410702A 2014;
  • Salameh BA, Leffler H, Nilsson UJ. 3-(1,2,3-Triazol-1-yl)-1-thio-galactosides as small, efficient, and hydrolytically stable inhibitors of galectin-3. Bioorg Med Chem Lett. 2005;15:3344–3346.
  • Öberg CT, Leffler H, Nilsson UJ. Arginine binding motifs: design and synthesis of galactose-derived arginine tweezers as galectin-3 inhibitors. J Med Chem. 2008;51:2297–2301.
  • Öberg CT, Noresson A-L, Leffler H, et al. Arene-anion based arginine-binding motif on a galactose scaffold: structure-activity relationships of interactions with arginine-rich galectins. Chem Eur J. 2011;17:8139–8144.
  • Rajput VK, Leffler H, Nilsson UJ, et al. Synthesis and evaluation of iminocoumaryl and coumaryl derivatized glycosides as galectin antagonists. Bioorg Med Chem Lett. 2014;24:3516–3520.
  • André S, Giguère D, Dam TK, et al. Synthesis and screening of a small glycomimetic library for inhibitory activity on medically relevant galactoside-specific lectins in assays of increasing biorelevance. New J Chem. 2010;34:2229.
  • Cumpstey I, Salomonsson E, Sundin A, et al. 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.
  • Cumpstey I, Salomonsson E, Sundin A, et al. Studies of arginine-arene interactions through synthesis and evaluation of a series of galectin-binding aromatic lactose esters. Chembiochem. 2007;8:1389–1398.
  • Ingrassia L, Nshimyumukiza P, Dewelle J, et al. A lactosylated steroid contributes in vivo therapeutic benefits in experimental models of mouse lymphoma and human glioblastoma. J Med Chem. 2006;49:1800–1807.
  • Glinsky GV, Price JE, Glinsky VV, et al. Inhibition of human breast cancer metastasis in nude mice by synthetic glycoamines. Cancer Res. 1996;56:5319–5324.
  • Glinsky VV, Glinsky GV, Rittenhouse-Olson K, et al. The role of Thomsen-Friedenreich antigen in adhesion of human breast and prostate cancer cells to the endothelium. Cancer Res. 2001;61:4851–4857.
  • Glinskii OV, Sud S, Mossine VV, et al. Inhibition of prostate cancer bone metastasis by synthetic TF antigen mimic/galectin-3 inhibitor lactulose-L-leucine. Neoplasia. 2012;14:65–73.
  • Glinsky VV, Kiriakova G, Glinskii OV, et al. Synthetic galectin-3 inhibitor increases metastatic cancer cell sensitivity to taxol-induced apoptosis in vitro and in vivo. Neoplasia. 2009;11:901–909.
  • Rabinovich GA, Cumashi A, Bianco G, et al. Synthetic lactulose amines: novel class of anticancer agents that induce tumor-cell apoptosis and inhibit galectin-mediated homotypic cell aggregation and endothelial cell morphogenesis. Glycobiology. 2006;16:210–220.
  • Stannard KA, Collins PM, Ito K, et al. Galectin inhibitory disaccharides promote tumour immunity in a breast cancer model. Cancer Lett. 2010;299:95–110.
  • Stowell SR, Qian Y, Karmakar S, et al. Differential roles of galectin-1 and galectin-3 in regulating leukocyte viability and cytokine secretion. J Immunol. 2008;180:3091–3102.
  • Delaine T, Cumpstey I, Ingrassia L, et al. Galectin-inhibitory thiodigalactoside ester derivatives have antimigratory effects in cultured lung and prostate cancer cells. J Med Chem. 2008;51:8109–8114.
  • Van Scherpenzeel M, Moret EE, Ballell L, et al. Synthesis and evaluation of new thiodigalactoside-based chemical probes to label galectin-3. ChemBioChem. 2009;10:1724–1733.
  • Takeuchi T, Tamura M, Nishiyama K, et al. Mammalian galectins bind Galactoseβ1–4Fucose disaccharide, a unique structural component of protostomial N-type glycoproteins. Biochem Biophys Res Commun. 2013;436:509–513.
  • Tejler J, Skogman F, Leffler H, et al. Synthesis of galactose-mimicking 1H-(1,2,3-triazol-1-yl)-mannosides as selective galectin-3 and 9N inhibitors. Carbohydr Res. 2007;342:1869–1875.
  • Öberg CT, Noresson A-L, Leffler H, et al. Synthesis of 3-amido-3-deoxy-β-d-talopyranosides: all-cis-substituted pyranosides as lectin inhibitors. Tetrahedron. 2011;67:9164–9172.
  • Collins PM, Oberg CT, Leffler H, et al. Taloside inhibitors of galectin-1 and galectin-3. Chem Biol Drug Des. 2012;79:339–346.
  • Kiessling L, Gestwicki JE, Strong L. Synthetic multivalent ligands in the exploration of cell-surface interactions. Curr Opin Chem Biol. 2000;4:696–703.
  • André S, Cejas Ortega PJ, Perez MA, et al. Lactose-containing starburst dendrimers: influence of dendrimer generation and binding-site orientation of receptors (plant/animal lectins and immunoglobulins) on binding properties. Glycobiology. 1999;9:1253–1261.
  • André S, Pieters RJ, Vrasidas I, et al. Wedgelike glycodendrimers as inhibitors of binding of mammalian galectins to glycoproteins, lactose maxiclusters, and cell surface glycoconjugates. ChemBioChem. 2001;2:822–830.
  • Vrasidas I, André S, Valentini P, et al. Rigidified multivalent lactose molecules and their interactions with mammalian galectins: a route to selective inhibitors. Org Biomol Chem. 2003;1:803–810.
  • André S, Kaltner H, Furuike T, et al. Persubstituted cyclodextrin-based glycoclusters as inhibitors of protein-carbohydrate recognition using purified plant and mammalian lectins and wild-type and lectin-gene-transfected tumor cells as targets. Bioconjug Chem. 2004;15:87–98.
  • André S, Sansone F, Kaltner H, et al. Calix[n]arene‐based glycoclusters: bioactivity of thiourea‐linked galactose/lactose moieties as inhibitors of binding of medically relevant lectins to a glycoprotein and cell‐surface glycoconjugates and selectivity among human adhesion/growth‐regulatory galectins. ChemBioChem. 2008;9:1649–1661.
  • Cecioni S, Matthews SE, Blanchard H, et al. Synthesis of lactosylated glycoclusters and inhibition studies with plant and human lectins. Carbohydr Res. 2012;356:132–141.
  • Gouin SG, García Fernández JM, Vanquelef E, et al. Multimeric lactoside “click clusters” as tools to investigate the effect of linker length in specific interactions with peanut lectin, galectin-1, and -3. Chem Eur J Chem Bio. 2010;11:1430–1442.
  • Giguère D, André S, Bonin M-A, et al. Inhibitory potential of chemical substitutions at bioinspired sites of β-d-galactopyranose on neoglycoprotein/cell surface binding of two classes of medically relevant lectins. Bioorg Med Chem. 2011;19:3280–3287.
  • Wang G-N, André S, Gabius H-J, et al. Bi- to tetravalent glycoclusters: synthesis, structure–activity profiles as lectin inhibitors and impact of combining both valency and headgroup tailoring on selectivity. Org Biomol Chem. 2012;10:6893.
  • Tejler J, Tullberg E, Frejd T, et al. Synthesis of multivalent lactose derivatives by 1,3-dipolar cycloadditions: selective galectin-1 inhibition. Carbohydr Res. 2006;341:1353–1362.
  • Klyosov A, Zomer E, Platt D DAVANAT ® (GM-CT-01) and colon cancer: preclinical and clinical (phase I and II) studies. ACS Symposium Series: American Chemical Society (ACS) 2012:89–130.
  • Blanchard H, Bum-Erdene K, Hugo MW. Inhibitors of galectins and implications for structure-based design of galectin-specific therapeutics. Aust J Chem. 2014;67:1763.
  • Blanchard H, Yu X, Collins PM, et al. Galectin-3 inhibitors: a patent review (2008-present). Expert Opin Ther Pat. 2014;24:1053–1065.
  • Mayo KH, Van Der Schaft DWJ, Griffioen AW. Designed beta-sheet peptides that inhibit proliferation and induce apoptosis in endothelial cells. Angiogenesis. 2001;4:45–51.
  • Wang JB, Wang MD, Li EX, et al. Advances and prospects of anginex as a promising anti-angiogenesis and anti-tumor agent. Peptides. 2012;38:457–462.
  • Mizukami Y, Jo W-S, Duerr E-M, et al. Induction of interleukin-8 preserves the angiogenic response in HIF-1alpha-deficient colon cancer cells. Nat Med. 2005;11:992–997.
  • Dings RP, Arroyo MM, Lockwood NA, et al. Beta-sheet is the bioactive conformation of the anti-angiogenic anginex peptide. Biochem J. 2003;373:281–288.
  • Arroyo MM, Mayo KH. NMR solution structure of the angiostatic peptide anginex. Biochim Biophys Acta (BBA) Proteins Proteom. 2007;1774:645–651.
  • Akerman ME, Pilch J, Peters D, et al. Angiostatic peptides use plasma fibronectin to home to angiogenic vasculature. Proc Natl Acad Sci. 2005;102:2040–2045.
  • Thijssen VL, Postel R, Brandwijk RJ, et al. Galectin-1 is essential in tumor angiogenesis and is a target for antiangiogenesis therapy. Proc Natl Acad Sci USA. 2006;103:15975–15980.
  • Griffioen AW, Van Der Schaft DW, Barendsz-Janson AF, et al. Anginex, a designed peptide that inhibits angiogenesis. Biochem J. 2001;354:233–242.
  • Van Der Schaft DW, Dings RP, De Lussanet QG, et al. The designer anti-angiogenic peptide anginex targets tumor endothelial cells and inhibits tumor growth in animal models. Faseb J. 2002;16:1991–1993.
  • Dings RPM, Van Laar ES, Webber J, et al. Ovarian tumor growth regression using a combination of vascular targeting agents anginex or topomimetic 0118 and the chemotherapeutic irofulven. Cancer Lett. 2008;265:270–280.
  • Dings RPM, Van Laar ES, Loren M, et al. Inhibiting tumor growth by targeting tumor vasculature with galectin-1 antagonist anginex conjugated to the cytotoxic acylfulvene, 6-hydroxylpropylacylfulvene. Bioconjug Chem. 2010;21:20–27.
  • Dings RP, Yokoyama Y, Ramakrishnan S, et al. The designed angiostatic peptide anginex synergistically improves chemotherapy and antiangiogenesis therapy with angiostatin. Cancer Res. 2003;63:382–385.
  • Amano M, Suzuki M, Andoh S, et al. Antiangiogenesis therapy using a novel angiogenesis inhibitor, anginex, following radiation causes tumor growth delay. Int J Clin Oncol. 2007;12:42–47.
  • Dings RP, Loren M, Heun H, et al. Scheduling of radiation with angiogenesis inhibitors anginex and Avastin improves therapeutic outcome via vessel normalization. Clin Cancer Res. 2007;13:3395–3402.
  • Brandwijk RJ, Nesmelova I, Dings RP, et al. Cloning an artificial gene encoding angiostatic anginex: from designed peptide to functional recombinant protein. Biochem Biophys Res Commun. 2005;333:1261–1268.
  • Brandwijk RJMGE, Dings RPM, Van Der Linden E, et al. Anti-angiogenesis and anti-tumor activity of recombinant anginex. Biochem Biophys Res Commun. 2006;349:1073–1078.
  • Mayo KH, Dings RP, Flader C, et al. Design of a partial peptide mimetic of anginex with antiangiogenic and anticancer activity. J Biol Chem. 2003;278:45746–45752.
  • Dings RP, Kumar N, Miller MC, et al. Structure-based optimization of angiostatic agent 6DBF7, an allosteric antagonist of galectin-1. J Pharmacol Exp Ther. 2013;344:589–599.
  • Dings RP, Chen X, Hellebrekers DM, et al. Design of nonpeptidic topomimetics of antiangiogenic proteins with antitumor activities. J Natl Cancer Inst. 2006;98:932–936.
  • Zucchetti M, Bonezzi K, Frapolli R, et al. Pharmacokinetics and antineoplastic activity of galectin-1-targeting OTX008 in combination with sunitinib. Cancer Chemother Pharmacol. 2013;72:879–887.
  • Dings RP, Levine JI, Brown SG, et al. Polycationic calixarene PTX013, a potent cytotoxic agent against tumors and drug resistant cancer. Invest New Drugs. 2013;31:1142–1150.
  • Salomonsson E, Thijssen VL, Griffioen AW, et al. The anti-angiogenic peptide anginex greatly enhances galectin-1 binding affinity for glycoproteins. J Biol Chem. 2011;286:13801–13804.
  • Dings RPM, Miller MC, Nesmelova I, et al. Antitumor agent calixarene 0118 targets human galectin-1 as an allosteric inhibitor of carbohydrate binding. J Med Chem. 2012;55:5121–5129.
  • Pilch J, Franzin CM, Knowles LM, et al. The anti-angiogenic peptide anginex disrupts the cell membrane. J Mol Biol. 2006;356:876–885.
  • Croci DO, Cerliani JP, Dalotto-Moreno T, et al. Glycosylation-dependent lectin- receptor interactions preserve angiogenesis in anti-VEGF refractory tumors. Cell. 2014;156:744–758.
  • Dalotto-Moreno T, Croci DO, Cerliani JP, et al. Targeting galectin-1 overcomes breast cancer-associated immunosuppression and prevents metastatic disease. Cancer Res. 2013;73:1107–1117.
  • Baum LG, Pang M, Perillo NL, et al. Human thymic epithelial cells express an endogenous lectin, galectin-1, which binds to core 2 O-glycans on thymocytes and T lymphoblastoid cells. J Exp Med. 1995;181:877–887.
  • Rabinovich GA, Ariel A, Hershkoviz R, et al. Specific inhibition of T-cell adhesion to extracellular matrix and proinflammatory cytokine secretion by human recombinant galectin-1. Immunology. 1999;97:100–106.
  • Levi G, Tarrab-Hazdai R, Teichberg VI. Prevention and therapy with electrolectin of experimental autoimmune myasthenia gravis in rabbits. Eur J Immunol. 1983;13:500–507.
  • Offner H, Celnik B, Bringman TS, et al. Recombinant human beta-galactoside binding lectin suppresses clinical and histological signs of experimental autoimmune encephalomyelitis. J Neuroimmunol. 1990;28:177–184.
  • Harjacek M, Diaz-Cano S, De Miguel M, et al. Expression of galectins-1 and -3 correlates with defective mononuclear cell apoptosis in patients with juvenile idiopathic arthritis. J Rheumatol. 2001;28:1914–1922.
  • Xibillé-Friedmann D, Bustos Rivera-Bahena C, Rojas-Serrano J, et al. A decrease in galectin-1 (Gal-1) levels correlates with an increase in anti-Gal-1 antibodies at the synovial level in patients with rheumatoid arthritis. Scand J Rheumatol. 2013;42:102–107.
  • Santucci L, Fiorucci S, Cammilleri F, et al. Galectin-1 exerts immunomodulatory and protective effects on concanavalin A-induced hepatitis in mice. Hepatology. 2000;31:399–406.
  • Santucci L, Fiorucci S, Rubinstein N, et al. Galectin-1 suppresses experimental colitis in mice. Gastroenterology. 2003;124:1381–1394.
  • Li S, Yu Y, Koehn CD, et al. Galectins in the pathogenesis of rheumatoid arthritis. J Clin Cell Immunol. 2013;4:1000164.
  • Kuo PL, Hung JY, Huang SK, et al. Lung cancer-derived galectin-1 mediates dendritic cell anergy through inhibitor of DNA binding 3/IL-10 signaling pathway. J Immunol. 2011;186:1521–1530.
  • Watanabe M, Takemasa I, Kaneko N, et al. Clinical significance of circulating galectins as colorectal cancer markers. Oncol Rep. 2011;25:1217–1226.
  • Saussez S, Glinoer D, Chantrain G, et al. Serum galectin-1 and galectin-3 levels in benign and malignant nodular thyroid disease. Thyroid. 2008;18:705–712.
  • Kim HJ, Jeon HK, Cho YJ, et al., et al. High galectin-1 expression correlates with poor prognosis and is involved in epithelial ovarian cancer proliferation and invasion. Eur J Cancer. 2012;48:1914–1921.
  • Kim HJ, Do IG, Jeon HK, et al., et al. Galectin 1 expression is associated with tumor invasion and metastasis in stage IB to IIA cervical cancer. Hum Pathol. 2013;44:62–68.
  • Solaro R, Chiellini F, Battisti A. Targeted delivery of protein drugs by nanocarriers. Materials. 2010;3:1928–1980.
  • Battig P, Saudan P, Gunde T, et al. Enhanced apoptotic activity of a structurally optimized form of galectin-1. Mol Immunol. 2004;41:9–18.
  • Bi S, Earl LA, Jacobs L, et al. Structural features of galectin-9 and galectin-1 that determine distinct. J Biol Chem. 2008;283:12248–12258.
  • Vertesy S, Michalak M, Miller MC, et al. Structural significance of galectin design: impairment of homodimer stability by linker insertion and partial reversion by ligand presence. Protein Eng Des Sel. 2015;28:199–210.
  • Earl LA, Bi S, Baum LG. Galectin multimerization and lattice formation are regulated by linker region structure. Glycobiology. 2011;21:6–12.
  • Cedeno-Laurent F, Barthel SR, Opperman MJ, et al. Development of a nascent galectin-1 chimeric molecule for studying the role of leukocyte galectin-1 ligands and immune disease modulation. J Immunol. 2010;185:4659–4672.
  • Wang CR, Shiau AL, Chen SY, et al. Intra-articular lentivirus-mediated delivery of galectin-3 shRNA and galectin-1 gene ameliorates collagen-induced arthritis. Gene Ther. 2010;17:1225–1233.
  • Weber W, Fussenegger M. Pharmacologic transgene control systems for gene therapy. J Gene Med. 2006;8:535–556.
  • Baum LG, Blackall DP, Arias-Magallano S, et al. Amelioration of graft versus host disease by galectin-1. Clin Immunol. 2003;109:295–307.
  • Nicolette CA, Fathman CG, Creusot R Transient expression of immunomodulatory polypeptides for the prevention and treatment of autoimmune disease, allergy and transplant rejection. US8513208B2 2013.
  • Tsai CY, Shiau AL, Chen SY, et al. Amelioration of collagen-induced arthritis in rats by nanogold. Arthritis Rheum. 2007;56:544–554.
  • Huang YJ, Shiau AL, Chen SY, et al. Multivalent structure of galectin-1-nanogold complex serves as potential therapeutics for rheumatoid arthritis by enhancing receptor clustering. Eur Cell Mater. 2012;23:170–181.
  • Claudia Oliveira IS, Veiga F, Ribeiro AJ. Recent advances in characterization of nonviral vectors for delivery of nucleic acids: impact on their biological performance. Expert Opin Drug Deliv. 2015;12:27–39.
  • Saie AA, Ray M, Mahmoudi M, et al. Engineering the nanoparticle-protein interface for cancer therapeutics. Cancer Treat Res. 2015;166:245–273.
  • Chatin B, Mevel M, Devalliere J, et al. Liposome-based formulation for intracellular delivery of functional proteins. Mol Ther Nucl Acids. 2015;4:e244.
  • Harris JM, Chess RB. Effect of pegylation on pharmaceuticals. Nat Rev Drug Discov. 2003;2:214–221.
  • Veronese FM, Harris JM. Introduction and overview of peptide and protein pegylation. Adv Drug Deliv Rev. 2002;54:453–456.
  • Kopitz J, Fik Z, André S, et al. Single-site mutational engineering and following MonoPEGylation of the human lectin galectin-2: effects on ligand binding, functional aspects, and clearance from serum. Mol Pharm. 2013;10:2054–2061.

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