title: 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.
authors.affiliation: Torrey Pines Institute for Molecular Studies, 3550 General Atomics Court, San Diego, California 92121, USA.
authors.forename: E
authors.initials: E
authors.lastname: Pérez-Payá
authors.forename: R A
authors.initials: RA
authors.lastname: Houghten
authors.forename: S E
authors.initials: SE
authors.lastname: Blondelle
mesh_terms: D000595:Amino Acid Sequence; D002384:Catalysis; D002942:Circular Dichroism; D016208:Databases, Factual; D019791:Guanidine; D006146:Guanidines; D007700:Kinetics; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D006146:Guanidines; D010455:Peptides; D011506:Proteins; D019791:Guanidine