Controlling the conformational stability of coiled-coil peptides with a single stereogenic center of a peripheral β-amino acid residue.

The key issue in the research on foldamers remains the understanding of the relationship between the monomers structure and conformational properties at the oligomer level. In peptidomimetic foldamers, the main goal of which is to mimic the structure of proteins, a main challenge is still better understanding of the folding of peptides and the factors that influence their conformational stability. We probed the impact of the modification of the peptide periphery with - and -2-aminocyclopentanecarboxylic acid (ACPC) on the structure and stability of the model coiled-coil using circular dichroism (CD), analytical ultracentrifugation (AUC) and two-dimensional nuclear magnetic resonance spectroscopy (2D NMR).

A computationally designed β-amino acid-containing miniprotein.

A new miniprotein built from three helices, including one structure based on the ααβαααβ sequence pattern was developed. Its crystal structure revealed a compact conformation with a well-packed hydrophobic core of unprecedented structure. The miniprotein formed dimers that were stabilized by the interaction of their hydrophobic surfaces.

Constrained beta-amino acid-containing miniproteins.

The construction of β-amino acid-containing peptides that fold to tertiary structures in solution remains challenging. Two model miniproteins, namely, Trp-cage and FSD, were scanned using a constrained β-amino acid in order to evaluate its impact on the folding process. Relationships between forces stabilizing the miniprotein structure and conformational stability of analogues were found.

Towards Foldameric Miniproteins: A Helix-Turn-Helix Motif.

Numerous beta-amino acid containing peptides forming secondary structures have been already described, however the design of higher-order structures remains poorly explored. The methodology allowing construction of sequence patterns containing few rigid secondary element was proposed and experimentally validated. On the basis of 9/10/9/12-helix containing cis-2-aminocyclopentanecarboxylic acid (cis-ACPC) residues arranged in an ααββ sequence pattern, a conformationally stable helix-turn-helix structure was designed.

Nuclear immunophilin FKBP39 from Drosophila melanogaster drives spontaneous liquid-liquid phase separation.

The FKBP39 from Drosophila melanogaster is a multifunctional regulatory immunophilin. It contains two globular domains linked by a highly charged disordered region. The N-terminal domain shows homology to the nucleoplasmin core domain, and the C-terminal domain is characteristic for the family of the FKBP immunophilin ligand binding domain.