α-hydrazino acid insertion governs peptide organization in solution by local structure ordering

Kavčič, Luka (author), Ilc, Gregor (author), Wang, Baifan (author), Vlahoviček-Kahlina, Kristina (author), Jerić, Ivanka (author), Plavec, Janez (author)

In this work, we have applied the concept of α-hydrazino acid insertion in a peptide sequence as a means of structurally organizing a potential protein−protein interactions (PPI) inhibitor. Hydrazino peptides characterized by the incorporation of an α-hydrazino acid at specific positions introduce an additional nitrogen atom into their backbone. This modification leads to a change in the electrostatic properties of the peptide and induces the restructuring of its hydrogen bonding network, resulting in conformational changes toward more stable structural motifs. Despite the successful use of synthetic hydrazino oligomers in binding to nucleic acids, the structural changes due to the incorporation of α-hydrazino acid into short natural peptides in solution are still poorly understood. Based on NMR data, we report structural models of p53-derived hydrazino peptides with elements of localized peptide structuring in the form of an α-, β-, or γ-turn as a result of hydrazino modification in the peptide backbone. The modifications could potentially lead to the preorganization of a helical secondary peptide structure in a solution that is favorable for binding to a biological receptor. Spectroscopically, we observed that the ensemble averaged rapidly interconverting conformations, including isomerization of the E−Z hydrazide bond. This further increases the adaptability by expanding the conformational space of hydrazine peptides as potential protein−protein interaction antagonists.

• Language: English
• Keywords: conformation, monomers, nuclear magnetic resonance spectroscopy, peptides, proteins, receptors
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FKKT - Faculty of Chemistry and Chemical Technology
• Publication status: Published
• Publication version: Version of Record
• Year: 2024
• Number of pages: Str. 22175–22185
• Numbering: Vol. 9, iss. 20
• PID: 20.500.12556/RUL-159457
• UDC: 577
• ISSN on article: 2470-1343
• DOI: 10.1021/acsomega.4c00804
• COBISS.SI-ID: 201310467
• Publication date in RUL: 10.07.2024

Record is a part of a journal

• Title: ACS omega
• Shortened title: ACS omega
• Publisher: American Chemical Society
• ISSN: 2470-1343
• COBISS.SI-ID: 525873945

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Secondary language

• Language: Slovenian
• Keywords: biokemija, nukleinske kisline, receptorji, hrbtenica, NMR