Pre-organization of the Core Structure of E-Selectin Antagonists (pages 1342–1351)
Dr. Daniel Schwizer, Dr. John T. Patton, Dr. Brian Cutting, Dr. Martin Smieško, Beatrice Wagner, Dr. Ako Kato, Dr. Céline Weckerle, Florian P. C. Binder, Dr. Said Rabbani, Dr. Oliver Schwardt, Dr. John L. Magnani and Prof. Beat Ernst
Article first published online: 30 DEC 2011 | DOI: 10.1002/chem.201102884
The gimmick with the mimic: A new class of N-acetyl-D-glucosamine (GlcNAc) mimics was incorporated into E-selectin antagonists. The test compounds and their 2′-benzoylated analogues exhibit affinities in the low micromolar range. STD-NMR suggests that the increase in affinity does not result from an additional hydrophobic contact of the alkyl substituent, but rather from a steric effect stabilizing the antagonist in its bioactive conformation (see figure).