The study examined how two short, fatty‑acid‑linked pieces of the human antimicrobial peptide LL‑37 (C12‑KR12 and C14‑KR12) stick to a negatively charged vanadium cluster (decavanadate). They bind mainly through charge attractions, and the vanadium cluster weakens the peptides’ helical shape, especially when heated.

Isothermal titration calorimetry (ITC), circular dichroism (CD) spectroscopy, and molecular dynamics simulations were applied to describe interactions between lipopeptides and decavanadate ions ([V₁₀O₂₈]^6-). The selected lipopeptides are conjugates of the amide of the KR12 peptide, the smallest antimicrobial peptide derived from human cathelicidin LL-37, with lauric acid (C12-KR12) and myristic acid (C14-KR12). The smaller sizes of C12-KR12 and C14-KR12 compared to proteins allow for the rigorous characterization of their non-covalent interactions with highly negatively charged [V₁₀O₂₈]^6- ions. The stoichiometry of the resulting decavanadate-peptide complexes and the thermodynamic parameters (&#x394;<i>G</i>, &#x394;<i>H</i>, and T&#x394;<i>S</i>) of the interactions were determined. The ITC results, supported by the MD simulation, showed that the binding of cationic lipopeptides for decavanadate is rather non-specific and is driven by enthalpic contributions resulting from electrostatic interactions between the positively charged residues of the peptides and the anionic decavanadate. Furthermore, the influence of temperature and the interactions with decavanadate ions on the stability of the &#x3b1;-helical structure of the lipopeptides were assessed based on CD spectra. Under the experimental conditions (50 mM sodium cacodylate buffer, pH 5), the peptides adopt an &#x3b1;-helical conformation, with C14-KR12 showing greater thermal stability. The interactions with vanadium species disrupt the &#x3b1;-helical structure and reduce its thermal stability.