FUNCTIONALIZED PROTEIN-LIKE STRUCTURES FROM CONFORMATIONALLY DEFINED SYNTHETIC COMBINATORIAL LIBRARIES

An approach is described for the de novo design of protein-like struct ures in which synthetic combinatorial libraries (SCLs) were incorporat ed into an amphipathic alpha-helical scaffold (an 18-mer sequence made up of leucine and lysine residues) to generate conformationally defin ed SCLs. In particular, the SCLs in which the ''combinatorialized'' po sitions were on the hydrophilic face showed an alpha-helical conformat ion in mild buffer. These SCLs were used to generate context-independe nt but position-dependent scales of alpha-helical propensity for the L -amino acids, These scales were then used to design highly alpha-helic al peptides that self-associated in mild buffer. The same approach was also found to permit the identification of conformation-dependent dec arboxylation catalysts.