The design and synthesis of a series of peptide derivatives based on a short ACE2 α-helix 1 epitope and subsequent [i - i+4] stapling of the secondary structure resulted in the identification of a 9-mer peptide capable to compete with recombinant ACE2 towards Spike RBD in the micromolar range. Specifically, SARS-CoV-2 Spike inhibitor screening based on colorimetric ELISA assay and structural studies by circular dichroism showed the ring-closing metathesis cyclization being capable to stabilize the helical structure of the 9-mer 34HEAEDLFYQ42 epitope better than the triazole stapling via click chemistry. MD simulations showed the stapled peptide being able not only to bind the Spike RBD, sterically interfering with ACE2, but also showing higher affinity to the target as compared to parent epitope.

Identification of a short ACE2-derived stapled peptide targeting the SARS-CoV-2 spike protein / Calugi, Lorenzo; Sautariello, Giulia; Lenci, Elena; Mattei, Mauro Leucio; Coppa, Crescenzo; Cini, Nicoletta; Contini, Alessandro; Trabocchi, Andrea. - In: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0223-5234. - ELETTRONICO. - 249:(2023), pp. 115118.0-115118.0. [10.1016/j.ejmech.2023.115118]

Identification of a short ACE2-derived stapled peptide targeting the SARS-CoV-2 spike protein

Calugi, Lorenzo;Sautariello, Giulia;Lenci, Elena;Mattei, Mauro Leucio;Trabocchi, Andrea
2023

Abstract

The design and synthesis of a series of peptide derivatives based on a short ACE2 α-helix 1 epitope and subsequent [i - i+4] stapling of the secondary structure resulted in the identification of a 9-mer peptide capable to compete with recombinant ACE2 towards Spike RBD in the micromolar range. Specifically, SARS-CoV-2 Spike inhibitor screening based on colorimetric ELISA assay and structural studies by circular dichroism showed the ring-closing metathesis cyclization being capable to stabilize the helical structure of the 9-mer 34HEAEDLFYQ42 epitope better than the triazole stapling via click chemistry. MD simulations showed the stapled peptide being able not only to bind the Spike RBD, sterically interfering with ACE2, but also showing higher affinity to the target as compared to parent epitope.
2023
249
0
0
Calugi, Lorenzo; Sautariello, Giulia; Lenci, Elena; Mattei, Mauro Leucio; Coppa, Crescenzo; Cini, Nicoletta; Contini, Alessandro; Trabocchi, Andrea
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1297280
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