Functionalized protein-like structures from conformationally defined synthetic combinatorial libraries.

Abstract

An approach is described for the de novo design of protein-like structures in which synthetic combinatorial libraries (SCLs) were incorporated into an amphipathic alpha-helical scaffold (an 18-mer sequence made up of leucine and lysine residues) to generate conformationally defined SCLs. In particular, the SCLs in which the "combinatorialized" positions were on the hydrophilic face showed an alpha-helical conformation in mild buffer. These SCLs were used to generate context-independent but position-dependent scales of alpha-helical propensity for the L-amino acids. These scales were then used to design highly alpha-helical peptides that self-associated in mild buffer. The same approach was also found to permit the identification of conformation-dependent decarboxylation catalysts.