10.1002/cbic.201700251
ChemBioChem
COMMUNICATION
4036-4040; c) J. M. Cousin, M. J. Cloninger, Beilstein J. Org. Chem.
2015, 11, 739-747.
innovative ligands with a conserved orientation supported by X-
ray crystallography. The alkyne-alkene modified LacNAc mimetic
1 proved to be a useful template as it allows the extension over
the carbohydrate recognition site to unexplored sub-pockets in a
predictable way. The alkene moiety did not interfere with sugar
binding and could be used in future experiments for covalent
conjugation with other compounds, e.g. drugs or biomarkers.
Furthermore, it could serve as a tool to establish multivalency to
compensate for the moderate affinity.
[8]
[9]
a) H. van Hattum, H. M. Branderhorst, E. E. Moret, U. J. Nilsson, H.
Leffler, R. J. Pieters, J. Med. Chem. 2013, 56, 1350-1354; b) D. Giguère,
S. André, M.-A. Bonin, M.-A. Bellefleur, A. Provencal, P. Cloutier, B.
Pucci, R. Roy, H.-J. Gabius, Bioorg. Med. Chem. 2011, 19, 3280-3287.
M. G. Ford, T. Weimar, T. Köhli, R. J. Woods, Proteins: Struct., Funct.,
Bioinf. 2003, 53, 229-240.
[10] a) M. F. López-Lucendo, D. Solís, S. André, J. Hirabayashi, K. Kasai, H.
Kaltner, H. J. Gabius, A. Romero, J. Mol. Biol. 2004, 343, 957-970; b) F.
P. Schwarz, K. D. Puri, R. G. Bhat, A. Surolia, J. Biol. Chem. 1993, 268,
7668-7677; c) C. Diehl, O. Engström, T. Delaine, M. Håkansson, S.
Genheden, K. Modig, H. Leffler, U. Ryde, U. J. Nilsson, M. Akke, J. Am.
Chem. Soc. 2010, 132, 14577-14589; d) H. Lis, N. Sharon, Chem. Rev.
1998, 98, 637-674.
Acknowledgements
We thank the team of beamline ID14-4 and ID 21-1 of ESRF
Grenoble, France for their excellent support during data collection.
[11] a) D. Andres, U. Gohlke, N. K. Broeker, S. Schulze, W. Rabsch, U.
Heinemann, S. Barbirz, R. Seckler, Glycobiology 2013, 23, 486-494; b)
K. Saraboji, M. Håkansson, S. Genheden, C. Diehl, J. Qvist, U.
Weininger, U. J. Nilsson, H. Leffler, U. Ryde, M. Akke, D. T. Logan,
Biochemistry 2012, 51, 296-306.
Keywords: galectin-1 • X-ray crystallography • carbohydrate-
lectin interaction • ligand design • fragment-based design
[12] D. I. Liao, G. Kapadia, H. Ahmed, G. R. Vasta, O. Herzberg, Proc. Natl.
Acad. Sci. U.S.A. 1994, 91, 1428-1432.
[1]
a) S. H. Barondes, D. N. W. Cooper, M. A. Gitt, H. Leffler, J. Biol. Chem.
1994, 269, 20807-20810; b) H. Leffler, S. Carlsson, M. Hedlund, Y. Qian,
F. Poirier, Glycoconjugate J. 2004, 19, 433-440.
[13] a) P. Sörme, P. Arnoux, B. Kahl-Knutsson, H. Leffler, J. M. Rini, U. J.
Nilsson, J. Am. Chem. Soc. 2005, 127, 1737-1743; b) P. Sörme, Y. N.
Qian, P. G. Nyholm, H. Leffler, U. J. Nilsson, ChemBioChem 2002, 3,
183-189; c) M. F. Marchiori, D. E. Pires Souto, L. Oliveira Bortot, J.
Francisco Pereira, L. T. Kubota, R. D. Cummings, M. Dias-Baruffi, I.
Carvalho, V. L. Campo, Bioorg. Med. Chem. 2015, 23, 3414-3425; d) T.-
J. Hsieh, H.-Y. Lin, Z. Tu, T.-C. Lin, S.-C. Wu, Y.-Y. Tseng, F.-T. Liu, S.-
T. D. Hsu, C.-H. Lin, Sci. Rep. 2016, 6, 29457.
[2]
[3]
a) F. T. Liu, G. A. Rabinovich, Nat. Rev. Cancer 2005, 5, 29-41; b) G. A.
Rabinovich, M. A. Toscano, Nat. Rev. Immunol. 2009, 9, 338-352.
a) N. L. Perillo, K. E. Pace, J. J. Seilhamer, L. G. Baum, Nature 1995,
378, 736-739; b) N. Rubinstein, M. Alvarez, N. W. Zwirner, M. A. Toscano,
J. M. Ilarregui, A. Bravo, J. Mordoh, L. Fainboim, O. L. Podhajcer, G. A.
Rabinovich, Cancer Cell 2004, 5, 241-251.
[4]
[5]
S. Punt, V. L. Thijssen, J. Vrolijk, C. D. de Kroon, A. Gorter, E. S.
Jordanova, PLoS One 2015, 10, e0129119.
[14] L. V. Lee, M. L. Mitchell, S. J. Huang, V. V. Fokin, K. B. Sharpless, C. H.
Wong, J. Am. Chem. Soc. 2003, 125, 9588-9589.
a) L. Astorgues-Xerri, M. E. Riveiro, A. Tijeras-Raballand, M. Serova, C.
Neuzillet, S. Albert, E. Raymond, S. Faivre, Cancer Treat. Rev. 2014, 40,
307-319; b) K. Smetana Jr., S. André, H. Kaltner, J. Kopitz, H.-J. Gabius,
Expert Opin. Ther. Targets 2013, 17, 379-392; c) M. Salatino, D. O. Croci,
G. A. Bianco, J. M. Ilarregui, M. A. Toscano, G. A. Rabinovich, Expert
Opin. Biol. Ther. 2008, 8, 45-57; d) D. J. Laderach, L. D. Gentilini, L.
Giribaldi, V. C. Delgado, L. Nugnes, D. O. Croci, N. Al Nakouzi, P. Sacca,
G. Casas, O. Mazza, M. A. Shipp, E. Vazquez, A. Chauchereau, J. L.
Kutok, S. J. Rodig, M. T. Elola, D. Compagno, G. A. Rabinovich, Cancer
Res. 2013, 73, 86-96; e) G. A. Rabinovich, Br. J. Cancer 2005, 92, 1188-
1192.
[15] a) V. V. Rostovtsev, L. G. Green, V. V. Fokin, K. B. Sharpless, Angew.
Chem. Int. Ed. 2002, 41, 2596-2599; b) C. W. Tornøe, C. Christensen,
M. Meldal, J. Org. Chem. 2002, 67, 3057-3064.
[16] a) T. Posner, Ber. Dtsch. Chem. Ges. 1905, 57, 646-657; b) C. E. Hoyle,
C. N. Bowman, Angew. Chem. Int. Ed. 2010, 49, 1540-1573.
[17] a) A. Fürstner, Angew. Chem. Int. Ed. 2000, 39, 3012-3043; b) R. H.
Grubbs, S. Chang, Tetrahedron 1998, 54, 4413-4450.
[18] A.-C. Knall, C. Slugovc, Chem. Soc. Rev. 2013, 42, 5131-5142.
[19] S. David, S. Hanessian, Tetrahedron 1985, 41, 643-663.
[20] a) C. A. Hunter, J. K. M. Sanders, J. Am. Chem. Soc. 1990, 112, 5525-
5534; b) C. Janiak, J. Chem. Soc. Dalton Trans. 2000, 3885-3896.
[21] K. Sonogashira, Y. Tohda, N. Hagihara, Tetrahedron Lett. 1975, 16,
4467-4470.
[6]
[7]
a) S. Saussez, F. Lorfevre, T. Lequeux, G. Laurent, G. Chantrain, F.
Vertongen, G. Toubeau, C. Decaestecker, R. Kiss, Oral Oncol. 2008, 44,
86-93; b) M. Watanabe, I. Takemasa, N. Kaneko, Y. Yokoyama, E.-I.
Matsuo, S. Iwasa, M. Mori, N. Matsuura, M. Monden, O. Nishimura,
Oncol. Rep. 2011, 25, 1217-1226.
[22] T. Ishida, R. Kobayashi, T. Yamada, Org. Lett. 2014, 16, 2430-2433.
[23] Y. F. Yong, J. A. Kowalski, M. A. Lipton, J. Org. Chem. 1997, 62, 1540-
1542.
a) S. Böcker, D. Laaf, L. Elling, Biomolecules 2015, 5, 1671; b) S. Zhang,
R.-O. Moussodia, C. Murzeau, H.-J. Sun, M. L. Klein, S. Vertesy, S.
Andre, R. Roy, H.-J. Gabius, V. Percec, Angew. Chem. Int. Ed. 2015, 54,
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