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. 2014 Sep 25;57(19):8056–8071. doi: 10.1021/jm500946r

Figure 3.

Figure 3

X-ray structure-based design of α,α-GM-LAMs. (A) Adjustment of the torsion angles about the (1→6) glycosidic linkage in the diglucosamine backbone of Lipid A upon binding by MD-2 results in a “twisted” orientation of the proximal GlcN ring for an agonist and in a coplanar orientation of the two GlcN rings for antagonist. (B) The proximal GlcN moiety of MD-2-bound E. coli Lipid A (PDB code 3FXI) adopts inclined orientation which allows the exposure of the 2-N-acyl chain.31 Image was generated with PyMol. (C) The molecular shape of α,α-trehalose (crystal structure)35,37 resembles the three-dimensional arrangement of βGlcN(1→6)GlcN backbone of the MD-2-bound E. coli Lipid A. (D) Structure of αGlcN(1↔1)αMan-based Lipid A mimetic (α,α-GM-LAM) 1 and proposed interaction of 1 with MD-2.