Using N-Myc61-89 as a starting point and through rational evaluation of the effects of sequence truncation, elongation and maleimide constraining we identified N-Myc73-94-N85C/G89C-mal as a relatively small, ligand efficient, constrained peptide with enhanced inhibitory potency when compared to its linear parent peptide. Correlation between potency (determined by competition FA) ad conformational analyses (by CD) indicated complex structure/activity relationships for the interaction of all the different N-Myc variants with Aurora-A, suggesting that α-helicity of the peptides does not solely determine inhibitory potency. Indeed, the most potent lead, N-Myc73-94-N85C/G89C-mal, was found to exhibit a unique CD spectrum; this may represent a maleimide-stabilized turn-like secondary structure although this could also arise from exciton coupling with the maleimide group, however the data is consistent with reduced random coil character. Overall, our results suggest that the constraint restricts the accessible conformational landscape of the peptide to an ensemble which is more compatible with recognition of Aurora-A. This in combination with enhanced helicity at the C-terminus, in Aurora-A bound complex and additional non-covalent contacts background ellipticity values were subtracted from raw sample ellipticity values (θ) when calculating mean residue ellipticities (MREs) using Equation :