A new class of N acetyl dglucosamine (GlcNAc) mimics for Eselectin antagonists was designed and synthesized. The mimic consists of a cyclohexane ring substituted with alkyl substituents adjacent to the linking position of the fucose moiety. Incorporation into E selectin antagonists led to the test compounds 8 and the 2’ benzoylated analogues 21 which exhibit affinities in the low micromolar range. By using saturation transfer difference (STD) NMR it could be shown that the increase in affinity does not result from an additional hydrophobic contact of the alkyl substituent with the target protein E selectin but rather from a steric effect stabilizing the antagonist in its bioactive conformation. The loss of affinity found for antagonists 10 and 35 containing a methyl substituent in a remote position (and therefore unable to support to the stabilization of the core) further supports this hypothesis. Finally when a GlcNAc mimetic containing two methyl substituents (52 and 53) was used in which one methyl was positioned adjacent to the fucose linking position and the other was in a remote position the affinity was regained.