| Title: |
Synthetic α-Helical Peptides as Potential Inhibitors of the ACE2 SARS-CoV-2 Interaction |
| Authors: |
Engelhardt, Pascal M.; Florez-Rueda, Sebastián; Drexelius, Marco; Neudörfl, Jörg-Martin; Lauster, Daniel; Hackenberger, Christian P. R.; Kühne, Ronald; Neundorf, Ines; Schmalz, Hans-Günther |
| Publication Year: |
2022 |
| Collection: |
FU Berlin: Refubium |
| Subject Terms: |
CD spectroscopy; peptides; protein-protein interactions; SARS-CoV-2; secondary structures; ddc:540 |
| Description: |
During viral cell entry, the spike protein of SARS-CoV-2 binds to the α1-helix motif of human angiotensin-converting enzyme 2 (ACE2). Thus, alpha-helical peptides mimicking this motif may serve as inhibitors of viral cell entry. For this purpose, we employed the rigidified diproline-derived module ProM-5 to induce α-helicity in short peptide sequences inspired by the ACE2 α1-helix. Starting with Ac-QAKTFLDKFNHEAEDLFYQ-NH2 as a relevant section of α1, a series of peptides, N-capped with either Ac-βHAsp-[ProM-5] or Ac-βHAsp-PP, were prepared and their α-helicities were investigated. While ProM-5 clearly showed a pronounced effect, an even increased degree of helicity (up to 63 %) was observed in sequences in which non-binding amino acids were replaced by alanine. The binding affinities of the peptides towards the spike protein, as determined by means of microscale thermophoresis (MST), revealed only a subtle influence of the α-helical content and, noteworthy, led to the identification of an Ac-βHAsp-PP-capped peptide displaying a very strong binding affinity (KD=62 nM). |
| Document Type: |
article in journal/newspaper |
| File Description: |
6 Seiten; application/pdf |
| Language: |
English |
| DOI: |
10.17169/refubium-35814 |
| DOI: |
10.1002/cbic.202200372 |
| Availability: |
https://refubium.fu-berlin.de/handle/fub188/36098; https://doi.org/10.17169/refubium-35814; https://doi.org/10.1002/cbic.202200372 |
| Rights: |
https://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.C4F3BF93 |
| Database: |
BASE |