Screening for galectin-3 inhibitors from synthetic lacto-N-biose libraries using microscale affinity chromatography coupled to mass spectrometry.

Abstract

The synthesis and screening of two beta-D-Galp-(1-3)-beta-d-GlcpN (lacto-N-biose) disaccharide libraries are reported. Solution-phase synthetic modifications at the HO-2' and NH positions were performed in an effort to enhance the affinity toward galectin-3, a galactose-binding protein involved in tumor metastasis, apoptosis, and inflammation. The libraries were screened for galectin-3 binding by microscale frontal affinity chromatography coupled to mass spectrometry (FAC/MS) allowing for rapid ranking of the different inhibitors and the determination of the galectin-3 binding Kd's. Compounds bearing a hydrophobic substituent on the NH group showed the highest affinity for the lectin. The N-naphthoyl derivative (Kd = 10.6 microM) was the best inhibitor with a 7 times increased affinity as compared to the N-acetyl parent compound (Kd = 73.3 microM).

• Authors: Sébastien Fort, Hyo-Sun Kim, Ole Hindsgaul
• Journal: The Journal of organic chemistry (J Org Chem) Vol. 71 Issue 19 Pg. 7146-54 (Sep 15 2006) ISSN: 0022-3263 [Print] United States
• PMID: 16958507 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Disaccharides
• Galectin 3
• Ligands
• galactosyl-1,3-N-acetylglucosamine
• Acetylglucosamine

Topics

• Acetylglucosamine (analogs & derivatives, chemical synthesis, chemistry)
• Chromatography, Affinity
• Disaccharides (chemical synthesis, chemistry)
• Galectin 3 (antagonists & inhibitors)
• Ligands
• Mass Spectrometry
• Molecular Structure
• Protein Binding