Heteronuclear ( 1 H-15 N) NOE values for lid residues 10-17 showed a significant increase following AM-7209 titration into WT MDM2, suggesting decreased mobility on the ps-ns timescale, consistent with ordering of this region (Figure ). Conversely, negligible or small increases in heteronuclear NOE values were observed for the equivalent lid residues following AM-7209 titration into the I19G mutant (Figure , see Figures for data for the entire protein sequences). In WT MDM2, residues 12-16 showed a trend towards negative secondary Ca chemical shifts upon AM-7209 addition, while residues 20-23 showed a trend towards positive Ca chemical shift (Figure , light purple and purple), consistent with increased b- strand and a-helical propensity, respectively. These trends were not observed when AM-7209 was titrated into a sample of I19G (Figure , light orange and orange). Upon addition of AM-7209 to WT MDM2 a trend towards negative secondary CO chemical shifts values was observed for residues 12-16 as opposed to the positive values observed for residues 20-23, which is again consistent with increased b-strand and a-helical propensity, respectively (Figure , light purple and purple). No such trends were observed when AM-7209 was added to the I19G mutant (Figure , light orange and orange).