Aromatic heterocycle galectin-1 interactions for selective single-digit nM affinity ligands

Kristoffer Peterson, Patrick M. Collins, Xiaoli Huang, Barbro Kahl-Knutsson, Sofia Essén, Fredrik R. Zetterberg, Stina Oredsson, Hakon Leffler, Helen Blanchard, Ulf J. Nilsson

Research output: Contribution to journalArticlepeer-review

3 Citations (SciVal)


A series of 3-triazole-thiogalactosides and 3,3′-triazole-thiodigalactosides substituted with different five-membered heterocycles at the C-4 triazole position were found to have high selectivity for galectin-1. Initial studies on the 3-triazole-thiogalactosides indicated that five membered heterocycles in general gave increased affinity for galectin-1 and improved selectivity over galectin-3. The selectivity profile was similar for thiodigalactosides exemplified by 3,3′ substituted thien-3-yltriazole and thiazol-2-yltriazole, both having single-digit nM galectin-1 affinity and almost 10-fold galectin-1 selectivity. The binding interactions of a thiodigalactoside based galectin-1 inhibitor with two thien-3-yltriazole moieties were studied with X-ray crystallography. One of the thiophene moieties was positioned deeper into the pocket than previously reported phenyltriazoles and formed close contacts with Val31, Ser29, Gly124, and Asp123. The affinity and structural analysis thus revealed that steric and electronic optimization of five-membered aromatic heterocycle binding in a narrow galectin-1 subsite confers high affinity and selectivity.

Original languageEnglish
Pages (from-to)24913-24922
Number of pages10
JournalRSC Advances
Issue number44
Publication statusPublished - 2018

Subject classification (UKÄ)

  • Biochemistry and Molecular Biology


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