Abstract
Invited for this month's cover picture is the group of Young Kee Kang at Chungbuk National University (Republic of Korea). The cover picture shows the preferred conformation of the hexamer of ϵ‐amino acid Amc5a with a cyclopentane substituent in the backbone investigated using DFT methods in chloroform and water. The Amc5a hexamer adopted a stable left‐handed conformation with a rise of 4.8 Å per turn both in chloroform and water. However, the hexamer of Ampa (an analogue of Amc5a with replacing cyclopentane by pyrrolidine) adopted different conformations in chloroform and in water. Read the full text of their Research Article at 10.1002/open.202100253.
“…Finding the appropriate protocol is a crucial step for conformational prediction of peptides and peptide foldamers in solution…” Find out more about the story behind the front cover research at 10.1002/open.202100253.
What is the most significant result of this study?
We predicted a new helical fold for oligomers of ϵ‐amino acid with a cyclopentane substituent in the backbone using DFT methods in chloroform and water. The most preferred conformation of oligomers (dimer to hexamer) was the left‐handed H16 helical structure both in chloroform and water. Four residues were found to be sufficient to induce the substantial H16 helix population in solution. However, the unsubstituted canonical ϵ‐residue dominantly exhibited a left‐handed H18 helical conformation in solution.
What prompted you to investigate this topic/problem?
It is well known that the polymer nylon 6 of the ϵ‐amino caproic acid forms fibrils composed of β‐sheet‐like chain structures. Polymer of ϵ‐ L‐lysine was first isolated from culture filtrates of Streptomyces albulus and is one of AMPs with antimicrobial activity against several human microbial pathogens. However, little was known about the conformational preference of ϵ‐oligopeptides studied by experimental and/or computational methods to date.
What are the main challenges in the broad area of your research?
Finding the appropriate protocol is a crucial step for conformational prediction of peptides and peptide foldamers in solution. We have focused on the assessment of various DFT methods for conformational study of peptides in solution (Chem. Phys. Lett. 2014, 600, 112; Chem. Phys. Lett. 2018, 702, 69; New J. Chem. 2021, 45, 9780). Based on these earlier results, we set up the appropriate protocol that can be used in conformational prediction of peptide foldamers in solution as reported in the present study.
What other topics are you working on at the moment?
Recently, we have focused on the study of peptide foldamers in solution using DFT methods and tried to predict the conformational preference whose experimental results are not available yet (ChemPlusChem
2021, 86, 533). We have designed the organocatalyst based on the helical folds and explored the feasible pathways for catalytic process. Peptide foldamers can adopt various helical structures, of which the type, handedness, and macrodipole direction of helices can be controlled by the substitutions and/or stereochemistry of the residues. In particular, we have focused on the impact of aza‐substutions in the backbone on the helical handedness in solution.
H. S. Park, Y. K. Kang, ChemistryOpen 2022, 11, e202200035.