Fig. 3. (A) In the crystal packing lipopeptides 5 and 7 adopt higher-ordered structures not observed with laspartomycin C. In this arrangement the lipids of both the lipopeptides and C10-P are oriented in the same direction while the peptide macrocycles interact to form a repeating trimer of dimers motif as indicated by the colored triangles. A proposed orientation of the multimeric assembly in the bacterial membrane (indicated with a grey gradient) is shown. (B) Interactions between the d-Dap9 and Asp4 residues present in lipopeptides 5 and 7, but absent in laspartomycin C, stabilize the trimer of dimers. (C) The presence of a hydrophobic core formed at the center of the trimer of dimers motif suggests that the side chain of Val10 present in the biologically more active lipopeptide 7 more optimally suits the steric requirements of this motif vs. the slightly bulkier Ile10 in lipopeptide 5. For clarity only major conformations are shown.
