Structure-Based Design of a Monosaccharide Ligand Targeting Galectin-8

Mohammad H. Bohari, Xing Yu, Chandan Kishor, Brijesh Patel, Rob Marc Go, Hadieh A. Eslampanah Seyedi, Yaron Vinik, I. Darren Grice, Yehiel Zick, Helen Blanchard

Research output: Contribution to journalArticlepeer-review


Galectin-8 is a -galactoside-recognising protein that has a role in the regulation of bone remodelling and is an emerging new target for tackling diseases with associated bone loss. We have designed and synthesised methyl 3-O-[1-carboxyethyl]--d-galactopyranoside (compound 6) as a ligand to target the N-terminal domain of galectin-8 (galectin-8N). Our design involved molecular dynamics (MD) simulations that predicted 6 to mimic the interactions made by the galactose ring as well as the carboxylic acid group of 3-O-sialylated lactose (3-SiaLac), with galectin-8N. Isothermal titration calorimetry (ITC) determined that the binding affinity of galectin-8N for 6 was 32.8m, whereas no significant affinity was detected for the C-terminal domain of galectin-8 (galectin-8C). The crystal structure of the galectin-8N-6 complex validated the predicted binding conformation and revealed the exact protein-ligand interactions that involve evolutionarily conserved amino acids of galectin and also those unique to galectin-8N for recognition. Overall, we have initiated and demonstrated a rational ligand design campaign to develop a monosaccharide-based scaffold as a binder of galectin-8.

Original languageEnglish
Pages (from-to)1664-1672
Number of pages9
Issue number16
StatePublished - 20 Aug 2018


Dive into the research topics of 'Structure-Based Design of a Monosaccharide Ligand Targeting Galectin-8'. Together they form a unique fingerprint.

Cite this