Arginine binding motifs: Design and synthesis of galactose-derived arginine tweezers as galectin-3 inhibitors

作者:Oberg Christopher T*; Leffler Hakon; Nilsson Ulf J
来源:Journal of Medicinal Chemistry, 2008, 51(7): 2297-2301.
DOI:10.1021/jm701266y

摘要

Anionic O2 derivatives of methyl 3-deoxy-3-(4-methylbenzamido)-1-thio-beta-D-galactopyranoside have been synthesized as inhibitors against galectin-3. The sulfate, H-phosphonate, and benzyl phosphate derivatives showed an increased affinity as compared to the parent unsubstituted galactopyranoside. Modeling revealed arginine-144 being pinched by the C3 benzamide and O2 anionic substituents in that the benzamide stacked face-to-face and the anionic O2 substituent ion-paired with the guanidinium moiety.

  • 出版日期2008-4-10