TY  - JOUR
AU  - Olajos, Gábor
AU  - Hetényi, Anasztázia
AU  - Wéber, Edit
AU  - Németh, Lukács
AU  - Szakonyi, Zsolt
AU  - Fülöp, Ferenc
AU  - Martinek, Tamás
TI  - Induced Folding of Protein-Sized Foldameric β-Sandwich Models with Core β-Amino Acid Residues
JF  - CHEMISTRY-A EUROPEAN JOURNAL
J2  - CHEM-EUR J
VL  - 21
PY  - 2015
IS  - 16
SP  - 6173
EP  - 6180
PG  - 8
SN  - 0947-6539
DO  - 10.1002/chem.201405581
UR  - https://m2.mtmt.hu/api/publication/2868602
ID  - 2868602
N1  - Funding Agency and Grant Number: Hungarian Academy of Sciences (Lendulet program) [LP-2011-009]; Gedeon Richter Plc. [TP7-017]; Hungarian Research Foundation [OTKA K112442]\n Funding text: This work was supported by the Hungarian Academy of Sciences (Lendulet program LP-2011-009), Gedeon Richter Plc. (TP7-017), and the Hungarian Research Foundation (OTKA K112442). Computations were carried out at the HPC Center of the University of Szeged (TAMOP-4.2.2.C-11/1/KONV-2012-0010).\n
Funding Agency and Grant Number: Hungarian Academy of Sciences (Lendulet program) [LP-2011-009]; Gedeon Richter Plc. [TP7-017]; Hungarian Research FoundationOrszagos Tudomanyos Kutatasi Alapprogramok (OTKA) [OTKA K112442]
            Funding text: This work was supported by the Hungarian Academy of Sciences (Lendulet program LP-2011-009), Gedeon Richter Plc. (TP7-017), and the Hungarian Research Foundation (OTKA K112442). Computations were carried out at the HPC Center of the University of Szeged (TAMOP-4.2.2.C-11/1/KONV-2012-0010).
CAplus AN 2015:484036; MEDLINE PMID: 25677195 (Journal; Article; Research Support, Non-U.S. Gov't);
AB  - 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. Dissolving sandwiches: A water-soluble β-sandwich has been constructed by using cyclic β-amino acids in the hydrophobic core (see figure). The structural stability is highly dependent on the side-chain, and the destructuring effects of the β-residues could be minimized by using (1R,2S)-2-aminocyclohexanecarboxylic acid. The β-sandwich displays protein-like thermal denaturation behavior.
LA  - English
DB  - MTMT
ER  -