α-Hydrazino Acid Insertion Governs Peptide Organization in Solution by Local Structure Ordering

Kavčič, Luka; Ilc, Gregor; Wang, Baifan; Vlahoviček-Kahlina, Kristina; Jerić, Ivanka; Plavec, Janez (2024) α-Hydrazino Acid Insertion Governs Peptide Organization in Solution by Local Structure Ordering. ACS Omega, 9 (20). pp. 22175-22185. ISSN 2470-1343

PDF - Published Version - article Available under License Creative Commons Attribution. Download (4MB)

Abstract

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.

Item Type:	Article
Uncontrolled Keywords:	conformation; monomers, nuclear magnetic resonance; peptides and proteins; receptors
Subjects:	NATURAL SCIENCES NATURAL SCIENCES > Chemistry NATURAL SCIENCES > Chemistry > Organic Chemistry
Divisions:	Division of Organic Chemistry and Biochemistry
Depositing User:	Ivanka Jerić
Date Deposited:	11 Dec 2025 12:14
URI:	http://fulir.irb.hr/id/eprint/10407
DOI:	10.1021/acsomega.4c00804

Actions (login required)

View Item