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 α-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 α-helical conformation in mild buffer. These SCLs were used to generate context-independent but position-dependent scales of α-helical propensity for the L-amino acids. These scales were then used to design highly α-helical peptides that self-associated in mild buffer. The same approach was also found to permit the identification of conformation- dependent decarboxylation catalysts.