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Bioactive Peptides and Their Metal Complexes as Novel Antimicrobial Agents

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Special Issue Information
Keywords
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A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Materials Chemistry".

Deadline for manuscript submissions: closed (31 May 2023) | Viewed by 6402

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Special Issue Editors

Dr. Denise Bellotti

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Guest Editor

Department of Environmental and Prevention Sciences, University of Ferrara, 44121 Ferrara, Italy
Interests: analytical chemistry; bioinorganic chemistry; coordination chemistry and metal complexes; peptides; solution equilibria

Prof. Dr. Maurizio Remelli

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Guest Editor

Department of Chemical and Pharmaceutical Sciences, University of Ferrara, Via L. Borsari 46, 44121 Ferrara, Italy
Interests: analytical chemistry; coordination chemistry and metal complexes; chemical thermodynamics; solution equilibria

Special Issue Information

Dear Colleagues,

At present, the scientific community is perfectly aware of the dramatic increase of antimicrobial-resistant infections. This phenomenon is well recognized as a serious threat and a scientific challenge that urgently needs to be solved. Current therapeutic treatments against infectious diseases are obsolete and often ineffective, highlighting the unquestionable necessity of new antimicrobial agents. Antimicrobial peptides (AMPs) represent a rational chance to overcome the current drug-resistance crisis, giving rise to a novel class of successful therapeutics, with many compounds already in the clinical trial phase.

This Special Issue aims to collect scientific papers focused on metal-related bioactive peptides; several studies have shown that metal ions can modulate the efficacy of various natural and synthetic AMPs, although a rational and unequivocal explanation of how exactly the metals participate in the expression of the antimicrobial activity has not been achieved.

A deep knowledge of the metal coordination chemistry, structural properties and biological activity of peptides could be crucial to the design of new effective metal-based antimicrobial drugs with adequate properties for clinical use. The aim of this Special Issue is to gather recent developments in the synthesis and characterization of metal–peptide complexes with promising antimicrobial properties and to examine their many potential applications.

Dr. Denise Bellotti
Prof. Dr. Maurizio Remelli
Guest Editors

Manuscript Submission Information

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Keywords

antimicrobial peptides
bioactive peptides
metal complexes
metallodrugs
peptide-based drugs
antimicrobial agents
peptide–metal interaction

Published Papers (4 papers)

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Research

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26 pages, 5699 KiB

Open AccessArticle

Characterization of Copper(II) and Zinc(II) Complexes of Peptides Mimicking the CuZnSOD Enzyme

by Enikő Székely, Mariann Molnár, Norbert Lihi and Katalin Várnagy

Molecules 2024, 29(4), 795; https://doi.org/10.3390/molecules29040795 - 8 Feb 2024

Viewed by 694

Abstract

Antimicrobial peptides are short cationic peptides that are present on biological surfaces susceptible to infection, and they play an important role in innate immunity. These peptides, like other compounds with antimicrobial activity, often have significant superoxide dismutase (SOD) activity. One direction of our research is the characterization of peptides modeling the CuZnSOD enzyme and the determination of their biological activity, and these results may contribute to the development of novel antimicrobial peptides. In the framework of this research, we have synthesized 10, 15, and 16-membered model peptides containing the amino acid sequence corresponding to the Cu(II) and Zn(II) binding sites of the CuZnSOD enzyme, namely the Zn(II)-binding HVGD sequence (80–83. fragments), the Cu(II)-binding sequence HVH (fragments 46–48), and the histidine (His63), which links the two metal ions as an imidazolate bridge: Ac-FHVHEGPHFN-NH₂ (L¹(10)), Ac-FHVHAGPHFNGGHVG-NH₂ (L²(15)), and Ac-FHVHEGPHFNGGHVGD-NH₂ (L³(16)). pH-potentiometric, UV-Vis-, and CD-spectroscopy studies of the Cu(II), Zn(II), and Cu(II)-Zn(II) mixed complexes of these peptides were performed, and the SOD activity of the complexes was determined. The binding sites preferred by Cu(II) and Zn(II) were identified by means of CD-spectroscopy. From the results obtained for these systems, it can be concluded that in equimolar solution, the –(NGG)HVGD- sequence of the peptides is the preferred binding site for copper(II) ion. However, in the presence of both metal ions, according to the native enzyme, the -HVGD- sequence offers the main binding site for Zn(II), while the majority of Cu(II) binds to the -FHVH- sequence. Based on the SOD activity assays, complexes of the 15- and 16-membered peptide have a significant SOD activity. Although this activity is smaller than that of the native CuZnSOD enzyme, the complexes showed better performance in the degradation of superoxide anion than other SOD mimics. Thus, the incorporation of specific amino acid sequences mimicking the CuZnSOD enzyme increases the efficiency of model systems in the catalytic decomposition of superoxide anion. Full article

(This article belongs to the Special Issue Bioactive Peptides and Their Metal Complexes as Novel Antimicrobial Agents)

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16 pages, 2421 KiB

Open AccessArticle

pH-Responsive Cobalt(II)-Coordinated Assembly Containing Quercetin for Antimicrobial Applications

by Giuseppina D. G. Santonoceta and Carmelo Sgarlata

Molecules 2023, 28(14), 5581; https://doi.org/10.3390/molecules28145581 - 22 Jul 2023

Cited by 1 | Viewed by 1065

Abstract

The development of novel drug delivery systems (DDSs) with promising antibacterial properties is essential for facing the emergency of increasing resistance to antimicrobial agents. The antibacterial features of quercetin and its metal complexes have been broadly investigated. However, several drawbacks affect their activity and effectiveness. In this work, we propose a DDS based on a pH-responsive cobalt(II)-coordinated assembly containing quercetin and polyacrylic acid. This system is suggested to trigger the release of the model drug in a pH-dependent mode by exploiting the localized acidic environment at the bacterial infection sites under anaerobic conditions. The delivery system has been designed by accurately examining the species and the multiple equilibria occurring in solution among the assembly components. The formation of cobalt(II) complexes with quercetin in the absence or presence of the pH-responsive polyacrylic acid was investigated in buffered aqueous solution at pH 7.4 using spectrophotometric (UV-Vis) and calorimetric (ITC) techniques. The determined binding affinities and thermodynamic parameters that resulted are essential for the development of a DDS with improved binding and release capabilities. Furthermore, the affinity of the polymer–cobalt(II) complex toward the model antimicrobial flavonoid was explored at the solid–liquid interface by quartz crystal microbalance (QCM-D) experiments, which provided marked evidence for drug loading and release under pH control. Full article

(This article belongs to the Special Issue Bioactive Peptides and Their Metal Complexes as Novel Antimicrobial Agents)

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Graphical abstract

14 pages, 2363 KiB

Open AccessArticle

CH vs. HC—Promiscuous Metal Sponges in Antimicrobial Peptides and Metallophores

by Kinga Garstka, Valentyn Dzyhovskyi, Joanna Wątły, Kamila Stokowa-Sołtys, Jolanta Świątek-Kozłowska, Henryk Kozłowski, Miquel Barceló-Oliver, Denise Bellotti and Magdalena Rowińska-Żyrek

Molecules 2023, 28(10), 3985; https://doi.org/10.3390/molecules28103985 - 9 May 2023

Cited by 2 | Viewed by 1503

Abstract

Histidine and cysteine residues, with their imidazole and thiol moieties that deprotonate at approximately physiological pH values, are primary binding sites for Zn(II), Ni(II) and Fe(II) ions and are thus ubiquitous both in peptidic metallophores and in antimicrobial peptides that may use nutritional immunity as a way to limit pathogenicity during infection. We focus on metal complex solution equilibria of model sequences encompassing Cys–His and His–Cys motifs, showing that the position of histidine and cysteine residues in the sequence has a crucial impact on its coordination properties. CH and HC motifs occur as many as 411 times in the antimicrobial peptide database, while similar CC and HH regions are found 348 and 94 times, respectively. Complex stabilities increase in the series Fe(II) < Ni(II) < Zn(II), with Zn(II) complexes dominating at physiological pH, and Ni(II) ones—above pH 9. The stabilities of Zn(II) complexes with Ac-ACHA-NH₂ and Ac-AHCA-NH₂ are comparable, and a similar tendency is observed for Fe(II), while in the case of Ni(II), the order of Cys and His does matter—complexes in which the metal is anchored on the third Cys (Ac-AHCA-NH₂) are thermodynamically stronger than those where Cys is in position two (Ac-ACHA-NH₂) at basic pH, at which point amides start to take part in the binding. Cysteine residues are much better Zn(II)-anchoring sites than histidines; Zn(II) clearly prefers the Cys–Cys type of ligands to Cys–His and His–Cys ones. In the case of His- and Cys-containing peptides, non-binding residues may have an impact on the stability of Ni(II) complexes, most likely protecting the central Ni(II) atom from interacting with solvent molecules. Full article

(This article belongs to the Special Issue Bioactive Peptides and Their Metal Complexes as Novel Antimicrobial Agents)

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Review

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19 pages, 2070 KiB

Open AccessReview

The Synergy between Zinc and Antimicrobial Peptides: An Insight into Unique Bioinorganic Interactions

by Caroline Donaghy, Jose Gabriel Javellana, Young-Jin Hong, Karrera Djoko and Alfredo M. Angeles-Boza

Molecules 2023, 28(5), 2156; https://doi.org/10.3390/molecules28052156 - 25 Feb 2023

Cited by 3 | Viewed by 2517

Abstract

Antimicrobial peptides (AMPs) are essential components of innate immunity across all species. AMPs have become the focus of attention in recent years, as scientists are addressing antibiotic resistance, a public health crisis that has reached epidemic proportions. This family of peptides represents a promising alternative to current antibiotics due to their broad-spectrum antimicrobial activity and tendency to avoid resistance development. A subfamily of AMPs interacts with metal ions to potentiate antimicrobial effectiveness, and, as such, they have been termed metalloAMPs. In this work, we review the scientific literature on metalloAMPs that enhance their antimicrobial efficacy when combined with the essential metal ion zinc(II). Beyond the role played by Zn(II) as a cofactor in different systems, it is well-known that this metal ion plays an important role in innate immunity. Here, we classify the different types of synergistic interactions between AMPs and Zn(II) into three distinct classes. By better understanding how each class of metalloAMPs uses Zn(II) to potentiate its activity, researchers can begin to exploit these interactions in the development of new antimicrobial agents and accelerate their use as therapeutics. Full article

(This article belongs to the Special Issue Bioactive Peptides and Their Metal Complexes as Novel Antimicrobial Agents)

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