title: Induced folding of protein-sized foldameric β-sandwich models with core β-amino acid residues.
abstract: The mimicry of protein-sized β-sheet structures with unnatural peptidic sequences (foldamers) is a considerable challenge. In this work, the de novo designed betabellin-14 β-sheet has been used as a template, and α→β residue mutations were carried out in the hydrophobic core (positions 12 and 19). β-Residues with diverse structural properties were utilized: Homologous β(3) -amino acids, (1R,2S)-2-aminocyclopentanecarboxylic acid (ACPC), (1R,2S)-2-aminocyclohexanecarboxylic acid (ACHC), (1R,2S)-2-aminocyclohex-3-enecarboxylic acid (ACEC), and (1S,2S,3R,5S)-2-amino-6,6-dimethylbicyclo[3.1.1]heptane-3-carboxylic acid (ABHC). Six α/β-peptidic chains were constructed in both monomeric and disulfide-linked dimeric forms. Structural studies based on circular dichroism spectroscopy, the analysis of NMR chemical shifts, and molecular dynamics simulations revealed that dimerization induced β-sheet formation in the 64-residue foldameric systems. Core replacement with (1R,2S)-ACHC was found to be unique among the β-amino acid building blocks studied because it was simultaneously able to maintain the interstrand hydrogen-bonding network and to fit sterically into the hydrophobic interior of the β-sandwich. The novel β-sandwich model containing 25 % unnatural building blocks afforded protein-like thermal denaturation behavior.
authors: Institute of Pharmaceutical Analysis, SZTE-MTA Lendület Foldamer Research Group, University of Szeged, 6720 Szeged (Hungary).
authors: Gábor
authors: G
authors: Olajos
authors: Anasztázia
authors: A
authors: Hetényi
authors: Edit
authors: E
authors: Wéber
authors: Lukács J
authors: LJ
authors: Németh
authors: Zsolt
authors: Z
authors: Szakonyi
authors: Ferenc
authors: F
authors: Fülöp
authors: Tamás A
authors: TA
authors: Martinek
mesh_terms: D000595:Amino Acid Sequence; D003509:Cyclohexanecarboxylic Acids / Q000737:chemistry; D003514:Cyclohexylamines / Q000737:chemistry; D003515:Cycloleucine / Q000737:chemistry; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D011489:Protein Denaturation; D017510:Protein Folding; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry*
chemical_list: D003509:Cyclohexanecarboxylic Acids; D003514:Cyclohexylamines; D011506:Proteins; D003515:Cycloleucine; C089955:betabellin 14; C103271:2-aminocyclohexanecarboxylic acid
keywords: amino acids; peptidomimetics; protein engineering; protein folding; protein structures