1H-1,2,3-Triazol-1-yl thiodigalactoside derivatives as high affinity galectin-3 inhibitors

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1H-1,2,3-Triazol-1-yl thiodigalactoside derivatives as high affinity galectin-3 inhibitors. / Salameh, Bader A.; Cumpstey, Ian; Sundin, Anders; Leffler, Hakon; Nilsson, Ulf.

I: Bioorganic & Medicinal Chemistry, Vol. 18, Nr. 14, 2010, s. 5367-5378.

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T1 - 1H-1,2,3-Triazol-1-yl thiodigalactoside derivatives as high affinity galectin-3 inhibitors

AU - Salameh, Bader A.

AU - Cumpstey, Ian

AU - Sundin, Anders

AU - Leffler, Hakon

AU - Nilsson, Ulf

N1 - The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Division of Microbiology, Immunology and Glycobiology - MIG (013025200), Organic chemistry (S/LTH) (011001240)

PY - 2010

Y1 - 2010

N2 - Galactose C3-triazole derivatives were synthesized by Cu(I)-catalyzed cycloaddition between acetylenes and galactose C3-azido derivatives. Evaluation against galectin-3, 7, 8N (N-terminal) and 9N (N-terminal) revealed 1,4-disubstituted triazoles to be high-affinity inhibitors of galectin-3 with selectivity over galectin-7, 8N, and 9N. Conformational analysis of 1,4-di-and 1,4,5-tri-substituted galactose C3-triazoles suggested that a triazole C5-substituent interfered sterically with the galectin proteins, which explained their poor affinities compared to the corresponding 1,4-disubstituted triazoles. Introduction of two 1,4-disubstituted triazole moieties onto thiodigalactoside resulted in affinities down to 29 nM for galectin-3. (C) 2010 Elsevier Ltd. All rights reserved.

AB - Galactose C3-triazole derivatives were synthesized by Cu(I)-catalyzed cycloaddition between acetylenes and galactose C3-azido derivatives. Evaluation against galectin-3, 7, 8N (N-terminal) and 9N (N-terminal) revealed 1,4-disubstituted triazoles to be high-affinity inhibitors of galectin-3 with selectivity over galectin-7, 8N, and 9N. Conformational analysis of 1,4-di-and 1,4,5-tri-substituted galactose C3-triazoles suggested that a triazole C5-substituent interfered sterically with the galectin proteins, which explained their poor affinities compared to the corresponding 1,4-disubstituted triazoles. Introduction of two 1,4-disubstituted triazole moieties onto thiodigalactoside resulted in affinities down to 29 nM for galectin-3. (C) 2010 Elsevier Ltd. All rights reserved.

KW - Galactose

KW - Inhibition

KW - Triazole

KW - Galectin

KW - Azide

U2 - 10.1016/j.bmc.2010.05.040

DO - 10.1016/j.bmc.2010.05.040

M3 - Article

C2 - 20538469

VL - 18

SP - 5367

EP - 5378

JO - Bioorganic and Medicinal Chemistry

JF - Bioorganic and Medicinal Chemistry

SN - 0968-0896

IS - 14

ER -