Induced Folding of Protein-Sized Foldameric β-Sandwich Models with Core β-Amino Acid Residues

Gábor Olajos, A. Hetényi, Edit Wéber, Lukács J. Németh, Z. Szakonyi, F. Fülöp, T. Martinek

Research output: Contribution to journalArticle

9 Citations (Scopus)

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 β3-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.

Original languageEnglish
Pages (from-to)6173-6180
Number of pages8
JournalChemistry - A European Journal
Volume21
Issue number16
DOIs
Publication statusPublished - Apr 13 2015

Fingerprint

Amino acids
Cycloleucine
Circular dichroism spectroscopy
Proteins
Heptanes
Amino Acids
Denaturation
Acids
Dimerization
Chemical shift
Carboxylic Acids
Disulfides
Molecular dynamics
Structural properties
Hydrogen bonds
Nuclear magnetic resonance
Computer simulation
Heptane
Carboxylic acids
Hot Temperature

Keywords

  • amino acids
  • peptidomimetics
  • protein engineering
  • protein folding
  • protein structures

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

Induced Folding of Protein-Sized Foldameric β-Sandwich Models with Core β-Amino Acid Residues. / Olajos, Gábor; Hetényi, A.; Wéber, Edit; Németh, Lukács J.; Szakonyi, Z.; Fülöp, F.; Martinek, T.

In: Chemistry - A European Journal, Vol. 21, No. 16, 13.04.2015, p. 6173-6180.

Research output: Contribution to journalArticle

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