Synthesis of O-galactosyl aldoximes as potent LacNAc-mimetic galectin-3 inhibitors

Johan Tejler; Hakon Leffler; Ulf J Nilsson

doi:10.1016/j.bmcl.2005.02.079

Synthesis of O-galactosyl aldoximes as potent LacNAc-mimetic galectin-3 inhibitors

Bioorg Med Chem Lett. 2005 May 2;15(9):2343-5. doi: 10.1016/j.bmcl.2005.02.079.

Authors

Johan Tejler¹, Hakon Leffler, Ulf J Nilsson

Affiliation

¹ Organic Chemistry, Lund University, PO Box 124, SE-221 00 Lund, Sweden.

PMID: 15837322
DOI: 10.1016/j.bmcl.2005.02.079

Abstract

A panel of anomeric oxime ether derivatives of beta-galactose were synthesized via the reaction of O-beta-D-galactopyranosylhydroxylamine with aldehydes. The oxime ethers were evaluated as inhibitors against galectin-3 in a competitive fluorescence polarization assay. The best inhibitor, [E]-O-(beta-D-galactopyranosyl)-indole-3-carbaldoxime (E-52), had a Kd value of 180 microM, which is 24 times better than methyl beta-D-galactopyranoside (Kd=4400 microM) and in the same range as methyl lactoside (Kd=220 microM).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Drug Design
Galactose / analogs & derivatives*
Galactose / chemical synthesis
Galactose / pharmacology
Galectin 3 / antagonists & inhibitors*
Isomerism
Kinetics
Molecular Conformation
Molecular Structure
Oximes / chemical synthesis*
Oximes / pharmacology
Structure-Activity Relationship

Substances

Galectin 3
Oximes
Galactose