Protein subtype-targeting through ligand epimerization: talose-selectivity of galectin-4 and galectin-8.
A series of O2 and O3-derivatized methyl beta-d-talopyranosides were synthesized and evaluated in vitro as inhibitors of the galactose-binding galectin-1, -2, -3, -4 (N- and C-terminal domains), 8 (N-terminal domain), and 9 (N-terminal domain). Galectin-4C and 8N were found to prefer the d-talopyranose configuration to the natural ligand d-galactopyranose configuration. Derivatization at talose O2 and/or O3 provided selective submillimolar inhibitors for these two galectins.
Oberg
Christopher T
CT
Organic Chemistry, Lund University, PO Box 124, SE-221 00 Lund, Sweden.
Blanchard
Helen
H
Leffler
Hakon
H
Nilsson
Ulf J
UJ
D001565:Benzoates / Q000737:chemistry*; D001665:Binding Sites; D005690:Galactose / Q000737:chemistry; D037483:Galectin 1 / Q000737:chemistry; D037502:Galectin 3 / Q000737:chemistry; D037541:Galectin 4 / Q000737:chemistry*; D037161:Galectins / Q000737:chemistry*; D006027:Glycosides / Q000737:chemistry*; D006801:Humans; D007783:Lactones / Q000737:chemistry*; D008024:Ligands; D008956:Models, Chemical; D015202:Protein Engineering / Q000379:methods; D017434:Protein Structure, Tertiary; D011714:Pyrans / Q000737:chemistry; D013050:Spectrometry, Fluorescence / Q000379:methods
D001565:Benzoates; D037483:Galectin 1; D037502:Galectin 3; D037541:Galectin 4; D037161:Galectins; D006027:Glycosides; C510913:L-talo-gamma-lactone; C091991:LGALS8 protein, human; C105032:LGALS9 protein, human; D007783:Lactones; D008024:Ligands; D011714:Pyrans; C572058:methyl 2-O-acetyl-3-O-toluoyltalopyranoside; D005690:Galactose