Cationic Peptides and Their Cu(II) and Ni(II) Complexes: Coordination and Biological Characteristics

Abstract

Antimicrobial peptides are a promising group of compounds used for the treatment of infections. In some cases, metal ions are essential to activate these molecules. Examples of metalloantibiotics are, for instance, bleomycin and dermcidin. This study is focused on three new pseudopeptides with potential biological activity. The coordination behavior of all ligands with Cu(II) and Ni(II) ions has been examined. Various analytical methods such as potentiometric titration, UV-Vis and CD spectroscopies, and mass spectrometry were used. All compounds are convenient chelators for metal ion-binding. Two of the ligands tested have histidine residues. Surprisingly, imidazole nitrogen is not involved in the coordination of the metal ion. The N-terminal amino group, Dab side chains, and amide nitrogen atoms of the peptide bonds coordinated Cu(II) and Ni(II) in all the complexes formed. The cytotoxicity of three pseudopeptides and their complexes was evaluated. Moreover, their other model allowed for assessing the attenuation of LPS-induced cytotoxicity and anti-inflammatory activities were also evaluated, the results of which revealed to be very promising.

Water‐Based Synthesis of β‐Sheet‐Like Supramolecular Metallohydrogel Organized by Using a Native Ultrashort Peptide Sequence

“…The blue shift in the maximum wavelength with increasing pH indicates that N amide of the peptide bonds gradually coordinates to Cu 2 + ions, and the concentration of the coordinated form, such as [N N-terminus , N imidazole , N amide ], increases at pH > 6. [16] This is in good agreement with the fact that HIT/Cu 2 + metallohydrogels are formed only at pH 4.0-6.0, and above pH 6, deep blue precipitation is observed and no gelation occurs (Figure S9). Therefore, in the higher pH region, the amides of HIT are used for coordination to Cu 2 + ions, and the β-sheet-like structure cannot be formed; consequently, no metallohydrogel is formed.…”

“…The CD spectra of HIT at pH < 4 (i. e., acidic conditions) show a maximum around 215 nm owing to the n!π* transition, regardless of the presence or absence of Cu 2 + ions. For example, the spectra at pH 1.88 (Figure S5 UV-Vis spectral analysis showed a trend similar to that of the CD analysis, with a maximum peak at 640-700 nm due to ligand-to-metal charge-transfer transitions [16] of HIT to Cu 2 + at pH 4-8 (Figure S6), indicating the formation of histamine-type [N N-terminus , N imidazole ] Cu 2 + /HIT 1 : 1 and 1 : 2 complexes [17] in this pH region (Figure S7). These results are consistent with the electrospray ionization time-of-flight mass spectra and 1 H NMR spectra of HIT/Cu 2 + (Figure S8 and S14).…”

“…UV‐Vis spectral analysis showed a trend similar to that of the CD analysis, with a maximum peak at 640–700 nm due to ligand‐to‐metal charge‐transfer transitions [16] of HIT to Cu 2+ at pH 4–8 (Figure S6), indicating the formation of histamine‐type [N N ‐terminus , N imidazole ] Cu 2+ /HIT 1 : 1 and 1 : 2 complexes [17] in this pH region (Figure S7). These results are consistent with the electrospray ionization time‐of‐flight mass spectra and 1 H NMR spectra of HIT/Cu 2+ (Figure S8 and S14).…”

Bioactive Peptides in Human Health and Disease

“…In another study, Kotynia and co-workers [ 5 ] identified three novel anti-microbial pseudopeptides containing the non-proteinogenic amino acids ornithine and 2,4-diaminobutyric acid. These pseudopeptides are metal chelators able to interact with copper and nickel ions.…”

Construction, Thermochemistry, and Fluorescence Properties of Novel Lanthanide Complexes Synthesized from Halogenated Aromatic Carboxylic Acids and Nitrogen-Containing Ligands

“…As an important branch of inorganic chemistry, coordination chemistry 1 is closely related to chemical fields such as organic chemistry 2 , analytical chemistry 3 , biochemistry 4 , medicinal chemistry 5 , and the chemical industry 6 . It has attracted the attention of many chemists.…”