Fig. 7. NMR conformers of analogue 5.

NMR restraints and ensemble of conformers corresponding to A5. a Side-chain amide region of the analogue 5 (¹H-NOESY experiment), with peak assignments. Amide/proton alpha (left) and amide/aromatic (right) regions of the analogue 5 (¹H-NOESY experiment), with peak assignments are shown as Supplementary Fig. 7a. 1D set of dilution experiments are included as Supplementary Fig. 7b. b Backbone superposition of the 15 lowest-energy calculated conformers. c Analogue 5, lowest energy conformer. Side chains are depicted as sticks. The residues defining the aromatic cluster are shown in yellow, the octanoyl moiety is highlighted in green whereas the remaining residues are shown in blue. The peptide backbone is shown in white. On the right, the equivalent Cortistatin conformer for comparison (shown in Fig. 1b). d Side chain and backbone distribution for the ensemble of the 15 best conformers shown as two orientations. Some residues are labelled. e Comparison of the pharmacophore region of analogue 5 to that of Cortistatin conformations represented in Fig. 1b. The comparison includes the distances between C-gamma atoms of the five residues considered to define the pharmacophore. The backbone and Chi1 comparison of these six molecules are provided as Supplementary Fig. 7c. Distances are represented as ranges to include the distance dispersion in the ensemble of conformations.