Synthesis of galactose-mimicking 1H-(1,2,3-triazol-1-yl)-mannosides as selective galectin-3 and 9N inhibitors.
1H-[1,2,3]-Triazol-1-yl mannosides have been synthesized as inhibitors for the beta-galactoside-binding family of galectin proteins. Easier synthetic access to C1 in mannose, as compared to C3 in galactose, for attachment of affinity-enhancing triazoles rendered a synthetic advantage. The best mannose-derived inhibitor for galectin-9N, 4-benzylaminocarbonyl-1H-[1,2,3]-triazol-1-yl beta-D-mannopyranoside, had a Kd value of 540 microM, which compares favorably with its galactoside counterpart (Kd=670 microM) and with LacNAc (Kd=500 microM).
Tejler
Johan
J
Organic Chemistry, Lund University, PO Box 124, SE-221 00 Lund, Sweden.
Skogman
Fredrik
F
Leffler
Hakon
H
Nilsson
Ulf J
UJ
D002236:Carbohydrate Conformation; D005690:Galactose / Q000737:chemistry* / Q000494:pharmacology; D037502:Galectin 3 / Q000037:antagonists & inhibitors*; D037161:Galectins / Q000037:antagonists & inhibitors*; D006865:Hydrogenation; D007202:Indicators and Reagents; D008362:Mannosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008958:Models, Molecular; D014230:Triazoles / Q000737:chemistry*
D037502:Galectin 3; D037161:Galectins; D007202:Indicators and Reagents; D008362:Mannosides; D014230:Triazoles; D005690:Galactose