Issue 23, 2024

Application of a modern theoretical approach to the study of the interaction of KR-12 peptides derived from human cathelicidins with Cu(ii) ions

Abstract

The human cationic antimicrobial protein (hCAP) corresponding to the overlapping sequences of 151–162 of hCAP named KR-12 peptide is the smallest portion of the only type of human Cathelicidin, which has been shown to be modifiable into a more effective antimicrobial. In this study, an in silico analysis, supported by potentiometric titration and isothermal titration calorimetry techniques, was performed to identify potential Cu(II) binding sites of KR-12. The analysis of the presented data at the given theoretical level (GFN2-xTB/ALPB) revealed which peptide chain fragments are involved in the most favourable KR-12–Cu(II) binding mode. Based on a quantum chemical approach, the most favourable coordination modes of Cu(II) to peptides are proposed together with the discussion of the chemical nature of the interactions. The presented results demonstrated that KR-12 interacts with metal ions mostly via the main chain's oxygen atoms; however, the two types of amino acids that are expected to be vital for the interaction of Cu(II) are D (aspartic acid) and R29 (arginine). It was demonstrated that in order to explain the complexity of the interaction process in peptide–metal ion systems, the use of theoretical methods is sometimes necessary to explain the details of the experimental results and provide an in-depth understanding of these dynamic systems.

Graphical abstract: Application of a modern theoretical approach to the study of the interaction of KR-12 peptides derived from human cathelicidins with Cu(ii) ions

Supplementary files

Article information

Article type
Paper
Submitted
08 Apr. 2024
Accepted
18 Maijs 2024
First published
20 Maijs 2024

Dalton Trans., 2024,53, 9942-9951

Application of a modern theoretical approach to the study of the interaction of KR-12 peptides derived from human cathelicidins with Cu(II) ions

J. Brzeski, D. Wyrzykowski and J. Makowska, Dalton Trans., 2024, 53, 9942 DOI: 10.1039/D4DT01027B

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