The analysis of the forces governing helix formation and stability in peptides and proteins has attracted considerable interest in order to shed light on folding mechanism. We analyzed the role of hydrophobic interaction, steric hindrance and chain length on i, i + 3 position in QK peptide, a VEGF mimetic helical peptide. We focused on position 10 of QK, occupied by a leucine, as previous studies highlighted the key role of the Leu7-Leu10 interaction in modulating the helix formation and inducing an unusual thermodynamic stability. Leu10 has been replaced by hydrophobic amino acids with different side-chain length, hydrophobicity and steric hindrance. Ten peptides were, hence, synthesized and analyzed combining circular dichroism, calorimetry and NMR spectroscopy. We found that helical content and thermal stability of peptide QK changed when Leu10 was replaced. Interestingly, we observed that the changes in the helical content and thermal stability were not always correlated and they depend on the type of interaction (strength and geometry) that could be established between Leu7 and the residue in position 10.

Probing the helical stability in a VEGF-mimetic peptide / L. De Rosa, D. Diana, R. Di Stasi, A. Romanelli, M.F.M. Sciacca, D. Milardi, C. Isernia, R. Fattorusso, L.D. D'Andrea. - In: BIOORGANIC CHEMISTRY. - ISSN 0045-2068. - 116(2021 Nov), pp. 105379.1-105379.8. [10.1016/j.bioorg.2021.105379]

Probing the helical stability in a VEGF-mimetic peptide

A. Romanelli;
2021

Abstract

The analysis of the forces governing helix formation and stability in peptides and proteins has attracted considerable interest in order to shed light on folding mechanism. We analyzed the role of hydrophobic interaction, steric hindrance and chain length on i, i + 3 position in QK peptide, a VEGF mimetic helical peptide. We focused on position 10 of QK, occupied by a leucine, as previous studies highlighted the key role of the Leu7-Leu10 interaction in modulating the helix formation and inducing an unusual thermodynamic stability. Leu10 has been replaced by hydrophobic amino acids with different side-chain length, hydrophobicity and steric hindrance. Ten peptides were, hence, synthesized and analyzed combining circular dichroism, calorimetry and NMR spectroscopy. We found that helical content and thermal stability of peptide QK changed when Leu10 was replaced. Interestingly, we observed that the changes in the helical content and thermal stability were not always correlated and they depend on the type of interaction (strength and geometry) that could be established between Leu7 and the residue in position 10.
Helical; Peptide; NMR spectroscopy; DSC; Circular dichroism
Settore CHIM/03 - Chimica Generale e Inorganica
21-ago-2021
Article (author)
File in questo prodotto:
File Dimensione Formato  
BioOrganic Chemistry2021 DeRosa_published.pdf

accesso riservato

Descrizione: articolo pubblicato
Tipologia: Publisher's version/PDF
Dimensione 2.31 MB
Formato Adobe PDF
2.31 MB Adobe PDF   Visualizza/Apri   Richiedi una copia
De Rosa et al revised_Bioorganic Chemistry 2021.pdf

accesso aperto

Tipologia: Pre-print (manoscritto inviato all'editore)
Dimensione 768.57 kB
Formato Adobe PDF
768.57 kB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/870147
Citazioni
  • ???jsp.display-item.citation.pmc??? 0
  • Scopus 1
  • ???jsp.display-item.citation.isi??? 1
social impact