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Mechanisms of Therapeutic Peptides
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Mechanisms of Therapeutic Peptides

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 (20 January 2023) | Viewed by 22584

Special Issue Editor

Prof. Dr. Christopher Jackson

E-Mail Website
Guest Editor
Sutton Arthritis Research Laboratory, Kolling Institute, University of Sydney at Royal North Shore Hospital, Sydney, Australia
Interests: inflammation; chronic wounds; rheumatoid arthritis; skin; activated protein C; matrix metalloproteinases
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Peptides are rapidly emerging as novel therapeutic drugs for a wide array of human diseases. There are more than 80 peptides approved by the FDA and many more new peptides currently under preclinical and clinical investigation.

Although there is no absolute cut-off to distinguish a peptide from a protein, it is generally considered that peptides are smaller than 50 amino acids. Peptides have advantages over larger proteins as therapeutics by being less expensive to produce and more amenable to the oral route of administration. Peptides also have therapeutic advantages over small molecule drugs, with their larger size allowing them to interact with target receptors having high affinity and specificity—for example, there are over 100 peptides that can act in this way on G protein-coupled receptors.

This Special Issue, entitled “Mechanisms of Therapeutic Peptides”, will include original research and review papers focusing on all mechanistic aspects relating to peptides which exert cytoprotective actions on cells, tissues, animal models, and/or human disease. These actions may include but are not limited to anti-inflammatory, antithrombotic, immunomodulatory, antimicrobial, and/or antioxidant activity. In addition to these mechanisms, preclinical/clinical studies may detail physical form/structural variants, pharmacokinetic parameters, dosages, route of administration, interaction with other drugs, contraindications, and/or side effects.

Prof. Dr. Christopher Jackson
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • peptides
  • therapeutic peptides
  • therapeutic drugs
  • proteins
  • cytoprotective actions

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Published Papers (5 papers)

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Research

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15 pages, 39546 KiB  
Article
Guanosine and Deoxyinosine Structural Analogs Extracted from Chick Early Amniotic Fluid Promote Cutaneous Wound Healing
by Mashaal Ahmad, Jia Yu, Sha Cheng, Zara Ahmad Khan, Yan Luo and Heng Luo
Int. J. Mol. Sci. 2023, 24(16), 12817; https://doi.org/10.3390/ijms241612817 - 15 Aug 2023
Cited by 2 | Viewed by 1947
Abstract
Wound healing is a complex, dynamic process supported by a myriad of cellular events that must be tightly coordinated to efficiently repair damaged tissue. These wounds are a significant socioeconomic burden due to their high prevalence and recurrence, which is why the phenomenon [...] Read more.
Wound healing is a complex, dynamic process supported by a myriad of cellular events that must be tightly coordinated to efficiently repair damaged tissue. These wounds are a significant socioeconomic burden due to their high prevalence and recurrence, which is why the phenomenon of wounds has also been labeled as a “Silent Epidemic”. Most of these wounds become “chronic”, with around 15% of them remaining unresolved 1-year post incidence, which results in a prolonged yet avoidable burden to patients, families, and the health system. In this experimental study, we tried to purify the potent components in chick early amniotic fluid (ceAF) and applied these components to the wound healing mechanism. We first subjected ceAF to a series of purifications, including an HPLC purification system along with ion-exchange chromatography technology to purify other potential components. Upon narrowing down, we found two structural analogs: guanosine and deoxyinosine. We performed these components’ cell scratch and trans-well migration assays to validate the accurate dosage. We also assessed these components via topical administration on the skin of murine model wounds. For this, we randomly divided C57BL/6 (all black, male, 5 weeks old) mice into groups. The wound model was established through excising the skin of mice and treated the wounds with different fractions of guanosine and deoxyinosine continuously for 8–10 day intervals. Once the healing was complete, the skin was excised to determine the inflammatory response and other biochemical parameters of the healed skin, including epidermal thickness, collagen density, macrophages, and neutrophil infiltration at the wounded site. Quantitative real-time PCR and immunoblot assays were performed to determine active gene expression and protein expression of proinflammatory molecules, growth factors, and cytokines. All these findings support our data indicating the promising healing properties of guanosine and deoxyinosine isolated from ceAF. Full article
(This article belongs to the Special Issue Mechanisms of Therapeutic Peptides)
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16 pages, 2221 KiB  
Article
De Novo Design of AC-P19M, a Novel Anticancer Peptide with Apoptotic Effects on Lung Cancer Cells and Anti-Angiogenic Activity
by Min Kyoung Shin, Bo-Young Jang, Kyung-Bin Bu, Seung-Ho Lee, Dong-Hee Han, Jin Wook Oh and Jung-Suk Sung
Int. J. Mol. Sci. 2022, 23(24), 15594; https://doi.org/10.3390/ijms232415594 - 9 Dec 2022
Cited by 19 | Viewed by 3006
Abstract
Despite the current developments in cancer therapeutics, efforts to excavate new anticancer agents continue rigorously due to obstacles, such as side effects and drug resistance. Anticancer peptides (ACPs) can be utilized to treat cancer because of their effectiveness on a variety of molecular [...] Read more.
Despite the current developments in cancer therapeutics, efforts to excavate new anticancer agents continue rigorously due to obstacles, such as side effects and drug resistance. Anticancer peptides (ACPs) can be utilized to treat cancer because of their effectiveness on a variety of molecular targets, along with high selectivity and specificity for cancer cells. In the present study, a novel ACP was de novo designed using in silico methods, and its functionality and molecular mechanisms of action were explored. AC-P19M was discovered through functional prediction and sequence modification based on peptide sequences currently available in the database. The peptide exhibited anticancer activity against lung cancer cells, A549 and H460, by disrupting cellular membranes and inducing apoptosis while showing low toxicity towards normal and red blood cells. In addition, the peptide inhibited the migration and invasion of lung cancer cells and reversed epithelial-mesenchymal transition. Moreover, AC-P19M showed anti-angiogenic activity through the inhibition of vascular endothelial growth factor receptor 2 signaling. Our findings suggest that AC-P19M is a novel ACP that directly or indirectly targets cancer cells, demonstrating the potential development of an anticancer agent and providing insights into the discovery of functional substances based on an in silico approach. Full article
(This article belongs to the Special Issue Mechanisms of Therapeutic Peptides)
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20 pages, 2889 KiB  
Article
Peptides Regulating Proliferative Activity and Inflammatory Pathways in the Monocyte/Macrophage THP-1 Cell Line
by Francesco Avolio, Stefano Martinotti, Vladimir Kh. Khavinson, Jessica Elisabetta Esposito, Giulia Giambuzzi, Antonio Marino, Ekaterina Mironova, Riccardo Pulcini, Iole Robuffo, Giuseppina Bologna, Pasquale Simeone, Paola Lanuti, Simone Guarnieri, Svetlana Trofimova, Antonio Domenico Procopio and Elena Toniato
Int. J. Mol. Sci. 2022, 23(7), 3607; https://doi.org/10.3390/ijms23073607 - 25 Mar 2022
Cited by 10 | Viewed by 7035
Abstract
This study evaluates the effects of five different peptides, the Epitalon® tetrapeptide, the Vilon® dipeptide, the Thymogen® dipeptide, the Thymalin® peptide complex, and the Chonluten® tripeptide, as regulators of inflammatory and proliferative processes in the human monocytic THP-1, [...] Read more.
This study evaluates the effects of five different peptides, the Epitalon® tetrapeptide, the Vilon® dipeptide, the Thymogen® dipeptide, the Thymalin® peptide complex, and the Chonluten® tripeptide, as regulators of inflammatory and proliferative processes in the human monocytic THP-1, which is a human leukemia monocytic cell line capable of differentiating into macrophages by PMA in vitro. These peptides (Khavinson Peptides®), characterized by Prof. Khavinson from 1973 onwards, were initially isolated from animal tissues and found to be organ specific. We tested the capacity of the five peptides to influence cell cultures in vitro by incubating THP-1 cells with peptides at certain concentrations known for being effective on recipient cells in culture. We found that all five peptides can modulate key proliferative patterns, increasing tyrosine phosphorylation of mitogen-activated cytoplasmic kinases. In addition, the Chonluten tripeptide, derived from bronchial epithelial cells, inhibited in vitro tumor necrosis factor (TNF) production of monocytes exposed to pro-inflammatory bacterial lipopolysaccharide (LPS). The low TNF release by monocytes is linked to a documented mechanism of TNF tolerance, promoting attenuation of inflammatory action. Therefore, all peptides inhibited the expression of TNF and pro-inflammatory IL-6 cytokine stimulated by LPS on terminally differentiated THP-1 cells. Lastly, by incubating the THP1 cells, treated with the peptides, on a layer of activated endothelial cells (HUVECs activated by LPS), we observed a reduction in cell adhesion, a typical pro-inflammatory mechanism. Overall, the results suggest that the Khavinson Peptides® cooperate as natural inducers of TNF tolerance in monocyte, and act on macrophages as anti-inflammatory molecules during inflammatory and microbial-mediated activity. Full article
(This article belongs to the Special Issue Mechanisms of Therapeutic Peptides)
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Review

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17 pages, 2016 KiB  
Review
Eptifibatide, an Older Therapeutic Peptide with New Indications: From Clinical Pharmacology to Everyday Clinical Practice
by Gašper Tonin and Jasna Klen
Int. J. Mol. Sci. 2023, 24(6), 5446; https://doi.org/10.3390/ijms24065446 - 13 Mar 2023
Cited by 12 | Viewed by 4961
Abstract
Therapeutic peptides are oligomers or short polymers of amino acids used for various medical purposes. Peptide-based treatments have evolved considerably due to new technologies, stimulating new research interests. They have been shown to be beneficial in a variety of therapeutic applications, notably in [...] Read more.
Therapeutic peptides are oligomers or short polymers of amino acids used for various medical purposes. Peptide-based treatments have evolved considerably due to new technologies, stimulating new research interests. They have been shown to be beneficial in a variety of therapeutic applications, notably in the treatment of cardiovascular disorders such as acute coronary syndrome (ACS). ACS is characterized by coronary artery wall damage and consequent formation of an intraluminal thrombus obstructing one or more coronary arteries, leading to unstable angina, non-ST elevated myocardial infarction, and ST-elevated myocardial infarction. One of the promising peptide drugs in the treatment of these pathologies is eptifibatide, a synthetic heptapeptide derived from rattlesnake venom. Eptifibatide is a glycoprotein IIb/IIIa inhibitor that blocks different pathways in platelet activation and aggregation. In this narrative review, we summarized the current evidence on the mechanism of action, clinical pharmacology, and applications of eptifibatide in cardiology. Additionally, we illustrated its possible broader usage with new indications, including ischemic stroke, carotid stenting, intracranial aneurysm stenting, and septic shock. Further research is, however, required to fully evaluate the role of eptifibatide in these pathologies, independently and in comparison to other medications. Full article
(This article belongs to the Special Issue Mechanisms of Therapeutic Peptides)
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16 pages, 711 KiB  
Review
The Screening of Therapeutic Peptides for Anti-Inflammation through Phage Display Technology
by Kangran Zhang, Yezhong Tang, Qin Chen and Yang Liu
Int. J. Mol. Sci. 2022, 23(15), 8554; https://doi.org/10.3390/ijms23158554 - 2 Aug 2022
Cited by 14 | Viewed by 4523
Abstract
For the treatment of inflammatory illnesses such as rheumatoid arthritis and carditis, as well as cancer, several anti-inflammatory medications have been created over the years to lower the concentrations of inflammatory mediators in the body. Peptides are a class of medication with the [...] Read more.
For the treatment of inflammatory illnesses such as rheumatoid arthritis and carditis, as well as cancer, several anti-inflammatory medications have been created over the years to lower the concentrations of inflammatory mediators in the body. Peptides are a class of medication with the advantages of weak immunogenicity and strong activity, and the phage display technique is an effective method for screening various therapeutic peptides, with a high affinity and selectivity, including anti-inflammation peptides. It enables the selection of high-affinity target-binding peptides from a complex pool of billions of peptides displayed on phages in a combinatorial library. In this review, we will discuss the regular process of using phage display technology to screen therapeutic peptides, and the peptides screened for anti-inflammation properties in recent years according to the target. We will describe how these peptides were screened and how they worked in vitro and in vivo. We will also discuss the current challenges and future outlook of using phage display to obtain anti-inflammatory therapeutic peptides. Full article
(This article belongs to the Special Issue Mechanisms of Therapeutic Peptides)
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