Galectins are glycoconjugate-binding lectins that via cross-linking of galactopyranose containing glycans are believed to influence e.g. glycoprotein trafficking, localization, residence times, which in turn may impact glycoprotein functions in cell proliferation, inflammatory processes, tumor growth, and tumor metastasis.[1] Consequently, this has sparked a growing interest in developing galectin agonist and antagonists as research tools and possibly drug leads.[2] Herein we will discuss our recent efforts towards the discovery and development of high-affinity and selective galectin-antagonizing analogs and mimetics of endogenous galectin ligand fragments with emphasis on aromatic-arginine interactions.[3] In addition, the use of such analogs and mimetics in evidencing the role galectin-3-glycan interactions in VEGFR2 signaling controlling angiogenesis[4] and in intracellular vesicular damage[5] will be presented. [1] aJ. W. Dennis, C. F. Brewer, Mol. Cell. Proteomics 2013, 12, 913-920; bS. Di Lella, V. Sundblad, J. Cerliani, C. M. Guardia, D. A. Estrin, G. R. Vasta, G. A. Rabinovich, Biochemistry 2011, 50, 7842-7857. [2] R. J. Pieters, ChemBioChem 2006, 7, 721-728. [3] aI. Cumpstey, E. Salomonsson, A. Sundin, H. Leffler, U. J. Nilsson, Chem. Eur. J. 2008, 14, 4233-4245; bI. Cumpstey, A. Sundin, H. Leffler, U. J. Nilsson, Angew. Chem. Int. Ed. 2005, 44, 5110-5112; cB. A. Salameh, I. Cumpstey, A. Sundin, H. Leffler, U. J. Nilsson, Bioorg. Med. Chem. 2010, 18, 5367-5378; dP. Sörme, P. Arnoux, B. Kahl-Knutsson, H. Leffler, J. M. Rini, U. J. Nilsson, J. Am. Chem. Soc. 2005, 127, 1737-1743. [4] W.-S. Chen, H. Leffler, U. J. Nilsson, N. Panjwani, FASEB J. 2013, 27, 828.821. [5] aG. Sharma, J. Stegmayr, M. C. Carlsson, U. J. Nilsson, S. Oredsson, H Leffler, 2014 ASCB-IFCB Meeting Abstract ID: 1751; bJ. Stegmayr, G. Sharma, M. Carlsson, S. Oredsson, U.J. Nilsson, H. Leffler, 2014 ASCB-IFCB Meeting Abstract ID 64.

Galectin-ligand analogs and mimetics in intracellular vesicle damage and in angiogenesis

249th National Meeting (2015)

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