Dissecting mechanism of coupled folding and binding of an intrinsically disordered protein by chemical synthesis of conformationally constrained analoguesElectronic supplementary information (ESI) available: Experimental protocols and Fig. S1-S41. See DOI: 10.1039/c7cc02276j

Non-canonical α-methyl amino acids were incorporated at various sites in the sequence of intrinsically disordered activation domain from the p160 transcriptional co-activator (ACTR) to facilitate the formation of α-helical structures. Kinetic and thermodynamic data confirm the induced fit mechanism of complex formation between the synthesized ACTR variants and the nuclear co-activator binding domain (NCBD). Non-canonical α-methyl amino acids were incorporated at various sites in the sequence of intrinsically disordered activation domain from the p160 transcriptional co-activator (ACTR) to facilitate the formation of α-helical structures.