Arginine binding motifs: design and synthesis of galactose-derived arginine tweezers as galectin-3 inhibitors.
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.
Oberg
Christopher T
CT
Organic Chemistry, Lund University, SE-221 00 Lund, Sweden.
Leffler
Hakon
H
Nilsson
Ulf J
UJ
D001120:Arginine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology; D001549:Benzamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001665:Binding Sites; D001667:Binding, Competitive; D015195:Drug Design; D005690:Galactose / Q000737:chemistry*; D005697:Galactosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D037502:Galectin 3 / Q000037:antagonists & inhibitors*; D008958:Models, Molecular; D008968:Molecular Conformation; D010100:Oxygen / Q000737:chemistry; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D001549:Benzamides; D005697:Galactosides; D037502:Galectin 3; D001120:Arginine; D010100:Oxygen; D005690:Galactose