C2-symmetrical thiodigalactoside bis-benzamido derivatives as high-affinity inhibitors of galectin-3: Efficient lectin inhibition through double arginine-arene interactions

Abstract

Inhibitors of galectin-3, which has been implicated in cancer- and immunity-related processes, can be synthesized from thiodigalactoside derivatives with aromatic amide substituents at both C3 positions (see structure). Dissociation constant (Kd) values as low as 33 nM have been obtained. Computer modeling suggests that such high affinity stems from double arginine-arene stacking interactions. (Chemical Equation Presented) © 2005 Wiley-VCH Verlag GmbH & Co. KGaA.