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Synthetic Peptides and Peptidomimetics: From Basic Science to Biomedical Applications—3rd Edition

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: closed (28 February 2025) | Viewed by 6469

Special Issue Editors

Special Issue Information

Dear Colleagues,

Synthetic peptides are gaining increasing interest as both research tools in basic and applied science and as therapeutic and diagnostic agents in clinical settings. Their use as inhibitors of protein–protein interactions is becoming a common practice toward elucidating the binding mode of proteins, advancing our understanding of signaling cascades, and offering a viable contribution to the design and development of new drugs. Synthetic peptides are also ideal ligands for extracellular receptors, acting as potent activators of several cellular pathways such as those of the immune response. To date, about 60 peptides have been approved for human use worldwide, many of which are derived from natural molecules, and hundreds more are progressing through the different stages of clinical trials. However, the poor membrane permeability, short plasma half-life, and scarce oral bioavailability strongly limit their druggability and negatively impact on clinical aspects. In this scenario, novel structural modifications are continuously sought for improving pharmacokinetic properties. Among others, amino acid or backbone modifications and the introduction of non-natural amino acids and conjugation of chemical moieties that extend the half-life, improve cellular uptake, stabilize active conformations, and modulate solubility are constantly proposed. Given the high biocompatibility, generally low toxicity, and functionalization potential, peptides and peptidomimetics are also being increasingly employed to develop new functional biomaterials which are excellent cell culture substrates for medicinal applications or that may act as biorecognition elements for the detection of analytes such as proteins, nucleic acids, and pathogens. In this instance, peptides are also being used as recognition units for chip-based biosensors for clinical diagnosis.

We therefore invite academic and industrial investigators working in all these fields to submit original research articles or reviews describing and discussing the most recent advancements and developments in basic science and biomedical applications.

Potential topics include, but are not limited to:

  • Synthetic peptides and peptidomimetics as protein–protein inhibitors
  • Synthetic procedures for preparing peptides and peptidomimetics
  • Biochemical and biophysical characterization of peptides and peptidomimetics
  • Peptide-based bioconjugation
  • Nanoparticle-conjugated peptides
  • Peptide-based bioreceptors
  • Peptide-based biomaterials

Dr. Nunzianna Doti
Dr. Menotti Ruvo
Guest Editors

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Published Papers (3 papers)

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Research

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18 pages, 3423 KiB  
Article
Integrating In Silico and In Vitro Approaches to Identify Natural Peptides with Selective Cytotoxicity against Cancer Cells
by Hui-Ju Kao, Tzu-Han Weng, Chia-Hung Chen, Yu-Chi Chen, Yu-Hsiang Chi, Kai-Yao Huang and Shun-Long Weng
Int. J. Mol. Sci. 2024, 25(13), 6848; https://doi.org/10.3390/ijms25136848 - 21 Jun 2024
Cited by 1 | Viewed by 1561
Abstract
Anticancer peptides (ACPs) are bioactive compounds known for their selective cytotoxicity against tumor cells via various mechanisms. Recent studies have demonstrated that in silico machine learning methods are effective in predicting peptides with anticancer activity. In this study, we collected and analyzed over [...] Read more.
Anticancer peptides (ACPs) are bioactive compounds known for their selective cytotoxicity against tumor cells via various mechanisms. Recent studies have demonstrated that in silico machine learning methods are effective in predicting peptides with anticancer activity. In this study, we collected and analyzed over a thousand experimentally verified ACPs, specifically targeting peptides derived from natural sources. We developed a precise prediction model based on their sequence and structural features, and the model’s evaluation results suggest its strong predictive ability for anticancer activity. To enhance reliability, we integrated the results of this model with those from other available methods. In total, we identified 176 potential ACPs, some of which were synthesized and further evaluated using the MTT colorimetric assay. All of these putative ACPs exhibited significant anticancer effects and selective cytotoxicity against specific tumor cells. In summary, we present a strategy for identifying and characterizing natural peptides with selective cytotoxicity against cancer cells, which could serve as novel therapeutic agents. Our prediction model can effectively screen new molecules for potential anticancer activity, and the results from in vitro experiments provide compelling evidence of the candidates’ anticancer effects and selective cytotoxicity. Full article
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10 pages, 1794 KiB  
Article
The Peptide AWRK6 Alleviates Lipid Accumulation in Hepatocytes by Inhibiting miR-5100 Targeting G6PC
by Jiaxin Liu, Ying Liu, Qiuyu Wang, Lili Jin and Dianbao Zhang
Int. J. Mol. Sci. 2023, 24(22), 16141; https://doi.org/10.3390/ijms242216141 - 9 Nov 2023
Viewed by 1566
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the leading chronic liver disease, with a worldwide prevalence of more than 25%, and there is no approved drug for NAFLD specifically. In our previous study, the synthetic peptide AWRK6 was found to ameliorate NAFLD in mice. [...] Read more.
Non-alcoholic fatty liver disease (NAFLD) is the leading chronic liver disease, with a worldwide prevalence of more than 25%, and there is no approved drug for NAFLD specifically. In our previous study, the synthetic peptide AWRK6 was found to ameliorate NAFLD in mice. However, the mechanisms involved are still largely unknown. Here, AWRK6 treatment presented an alleviative effect on lipid accumulation induced by oleic acid in hepatocytes. Meanwhile, miR-5100 and miR-505 were found to be elevated by oleic acid induction and reversed by AWRK6 incubation. Further, the miR-5100 inhibitor inhibited oleic acid-induced lipid accumulation, and the alleviation effect of AWRK6 was partially counteracted by miR-5100 mimics. The screening of potential target genes revealed that a catalytic subunit of G6Pase G6PC was significantly inhibited by miR-5100 mimics transfection in both mRNA and protein levels. The direct targeting of miR-5100 on G6PC was verified by a Dual-Luciferase Reporter Assay. Moreover, the mRNA and protein levels of G6PC were found to be significantly increased by AWRK6 treatment. These results suggested that the peptide AWRK6 could alleviate lipid accumulation in hepatocytes, partly through reducing miR-5100 to restore one of its targets: G6PC. Thus, AWRK6 has the potential to treat NAFLD. Additionally, miR-5100 is a mediator of lipid accumulation in hepatocytes, which could be targeted by AWRK6. Full article
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Review

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30 pages, 2545 KiB  
Review
Overview of Epitalon—Highly Bioactive Pineal Tetrapeptide with Promising Properties
by Szymon Kamil Araj, Jakub Brzezik, Katarzyna Mądra-Gackowska and Łukasz Szeleszczuk
Int. J. Mol. Sci. 2025, 26(6), 2691; https://doi.org/10.3390/ijms26062691 - 17 Mar 2025
Viewed by 2773
Abstract
Epitalon, also known as Epithalon or Epithalone, is a tetrapeptide, Ala-Glu-Asp-Gly (AEDG), which was synthesized based on the amino acids composition of Epithalamin, a bovine pineal gland extract, prior to its discovery in pineal gland polypeptide complex solution. During the last 25 years, [...] Read more.
Epitalon, also known as Epithalon or Epithalone, is a tetrapeptide, Ala-Glu-Asp-Gly (AEDG), which was synthesized based on the amino acids composition of Epithalamin, a bovine pineal gland extract, prior to its discovery in pineal gland polypeptide complex solution. During the last 25 years, this compound has been extensively studied using in vitro, in vivo, and in silico methods. The results of these studies indicate significant geroprotective and neuroendocrine effects of Epitalone, resulting from its antioxidant, neuro-protective, and antimutagenic effects, originating from both specific and nonspecific mechanisms. Although it has been demonstrated that Epitalon exerts, among other effects, a direct influence on melatonin synthesis, alters the mRNA levels of interleukin-2, modulates the mitogenic activity of murine thymocytes, and enhances the activity of various enzymes, including AChE, BuChE, and telomerase, it remains uncertain whether these are the sole mechanisms of action of this compound. Moreover, despite the considerable volume of research on the biological and pharmacodynamic characteristics of Epitalon, the quantity of physico-chemical and structural investigations of this peptide remains quite limited. This review aims to conclude the most important findings from such studies, thus presenting the current state of knowledge on Epitalon. Full article
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