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Pharmaceutics
Special Issues
Pharmaceutical Applications of Bioactive Peptides
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Pharmaceutical Applications of Bioactive Peptides

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Biologics and Biosimilars".

Deadline for manuscript submissions: closed (31 May 2021) | Viewed by 18750

Special Issue Editor

Prof. Dr. Giancarlo Morelli

E-Mail Website
Guest Editor
1. Department of Pharmacy, University of Naples “Federico II”, Via Domenico Montesano 49, 80131 Naples, Italy
2. Research Centre on Bioactive Peptides (CIRPeB), University of Naples “Federico II”, 80134 Naples, Italy
Interests: bioactive peptides; modified peptides as diagnostic and therapeutics; aggregating peptides; peptide materials; active drug delivery promoted by peptides
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

For many years, bioactive peptides have been attracting significant interest for their ability to promote biological processes and, therefore, their application as pharmaceutical agents.

Over 60 peptide drugs are approved in the United States and other major markets, and peptides continue to enter in clinical development phases. Over 150 peptides are in active development today for different applications, targeting different biological counterparts, and covering several therapeutic areas.

This Special Issue will describe new biologically active peptides and their modified forms (cyclic, conjugated, pegylated, alkylated peptides, and peptides containing non-coded residues) that are very close to pharmaceutical development. The in-vitro and in-vivo results will demonstrate their pharmacological efficacy. All therapeutical areas, including oncology, metabolic diseases, cardiovascular diseases, antimicrobial therapy, endocrinology, and so on, will be covered. Moreover, this Special Issue will also cover pharmaceutical peptides that act as in-vivo diagnostics (labeled peptides, radioactive peptides) or theranostics for dual-use as in-vivo diagnostics and therapeutics. Peptides isolated from natural sources or de-novo designed and chemically synthesized will be considered for this Special Issue.

Prof. Dr. Giancarlo Morelli
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. Pharmaceutics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). 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

  • Pharmaceutical bioactive peptides
  • Therapeutic peptides
  • Peptides as diagnostics
  • Peptide as theranostics
  • Labeled pharmaceutical peptides
  • Antimicrobial peptides
  • Peptide mimetics
  • Chemical bioconjugation of pharmaceutical peptides

Published Papers (6 papers)

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Research

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15 pages, 2590 KiB  
Article
The Effects of pH and Excipients on Exenatide Stability in Solution
by Alexander Benet, Troy Halseth, Jukyung Kang, April Kim, Rose Ackermann, Santhanakrishnan Srinivasan, Steven Schwendeman and Anna Schwendeman
Pharmaceutics 2021, 13(8), 1263; https://doi.org/10.3390/pharmaceutics13081263 - 16 Aug 2021
Cited by 10 | Viewed by 3239
Abstract
Exenatide, a glucagon-like peptide-1 receptor agonist, is the active pharmaceutical ingredient in Byetta® and Bydureon®, two type 2 diabetes drug products that have generics and multiple follow-up formulations currently in development. Even though exenatide is known to be chemically and [...] Read more.
Exenatide, a glucagon-like peptide-1 receptor agonist, is the active pharmaceutical ingredient in Byetta® and Bydureon®, two type 2 diabetes drug products that have generics and multiple follow-up formulations currently in development. Even though exenatide is known to be chemically and physically unstable at pH 7.5, there lacks a systematic evaluation of the impact of pH and excipients on the peptide solution stability. In this study, we established analytical methods to measure the chemical and physical degradation of the peptide in solution. Exenatide remained relatively stable at pH 4.5 when incubated at 37 °C. At pH 5.5–6.5, degradation was driven by oxidation, while driven by deamidation at pH 7.5–8.5. Significant aggregation of exenatide at pH 7.5 and 8.5 was detected by size exclusion chromatography and dynamic light scattering. Each pH value greater than 4.5 exhibited unique profiles corresponding to a loss of α-helical content and an increase in unordered structures. The addition of sugars, including mannitol, sorbitol and sucrose, conferred small protective effects against peptide aggregation when incubating at pH 7.5 and 37 °C, as measured by size-exclusion chromatography and dynamic light scattering. The results of this study will be useful for investigators developing generic exenatide products, peptide analogs and novel exenatide drug delivery systems. Full article
(This article belongs to the Special Issue Pharmaceutical Applications of Bioactive Peptides)
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17 pages, 3254 KiB  
Article
Interaction of a Short Peptide with G-Quadruplex-Forming Sequences: An SRCD and CD Study
by Claudia Honisch, Eugenio Ragazzi, Rohanah Hussain, John Brazier, Giuliano Siligardi and Paolo Ruzza
Pharmaceutics 2021, 13(8), 1104; https://doi.org/10.3390/pharmaceutics13081104 - 21 Jul 2021
Cited by 6 | Viewed by 3297
Abstract
G-quadruplex (G4) forming DNA sequences were recently found to play a crucial role in the regulation of genomic processes such as replication, transcription and translation, also related to serious diseases. Therefore, systems capable of controlling DNA and RNA G-quadruplex structures would be useful [...] Read more.
G-quadruplex (G4) forming DNA sequences were recently found to play a crucial role in the regulation of genomic processes such as replication, transcription and translation, also related to serious diseases. Therefore, systems capable of controlling DNA and RNA G-quadruplex structures would be useful for the modulation of various cellular events. In particular, peptides represent good candidates for targeting G-quadruplex structures, since they are easily tailored to enhance their functionality. In this work, we analyzed, by circular dichroism and synchrotron radiation circular dichroism spectroscopies, the interaction of a 25-residue peptide deriving from RHAU helicases (Rhau25) with three G-quadruplex-forming oligonucleotide sequences, in both sodium- and potassium-containing buffers, the most relevant monovalent cations in physiological conditions. The peptide displayed greater affinity for the G4 sequences adopting a parallel structure. However, it showed the ability to also interact with antiparallel or hybrid G-quadruplex structures, inducing a conformation conversion to the parallel structure. The stability of the oligonucleotide structure alone or in presence of the Rhau25 peptide was studied by temperature melting and UV denaturation experiments, and the data showed that the interaction with the peptide stabilized the conformation of oligonucleotide sequences when subjected to stress conditions. Full article
(This article belongs to the Special Issue Pharmaceutical Applications of Bioactive Peptides)
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14 pages, 1943 KiB  
Article
Structure–Activity Relationship and Molecular Docking of a Kunitz-Like Trypsin Inhibitor, Kunitzin-AH, from the Skin Secretion of Amolops hainanensis
by Yuqing Chen, Xinping Xi, Chengbang Ma, Mei Zhou, Xiaoling Chen, Zhuming Ye, Lilin Ge, Qinan Wu, Tianbao Chen, Lei Wang and Hang Fai Kwok
Pharmaceutics 2021, 13(7), 966; https://doi.org/10.3390/pharmaceutics13070966 - 26 Jun 2021
Cited by 4 | Viewed by 2025
Abstract
Kunitz-like trypsin inhibitors are one of the most noteworthy research objects owing to their significance in pharmacological studies, including anticarcinogenic activity, obesity regulation and anticoagulation. In the current study, a novel Kunitz-like trypsin inhibitor, Kunitzin-AH, was isolated from the skin secretion of Amolops [...] Read more.
Kunitz-like trypsin inhibitors are one of the most noteworthy research objects owing to their significance in pharmacological studies, including anticarcinogenic activity, obesity regulation and anticoagulation. In the current study, a novel Kunitz-like trypsin inhibitor, Kunitzin-AH, was isolated from the skin secretion of Amolops hainanensis. The novel peptide displayed a modest trypsin inhibitory activity with the inhibitor constant (Ki) value of 1.18 ± 0.08 µM without inducing damage to healthy horse erythrocytes. Then, a series of shortened variants of Kunitzin-AH were designed by truncating a peptide loop and site mutation inside the loop to illustrate the structure–activity relationship of the trypsin inhibition function. Among the variants, a significant decrease was observed for the Cys-Cys loop domain, while the extension of an Arg at N-terminus (RCKAAFC) retained the inhibitory activity, indicating that the -RCK-motif is essential in forming the reactive domain for exerting the inhibitory activity. Furthermore, substitutions of Ala by hydrophobic or hydrophilic residues decreased the activity, indicating suitable steric hindrance provides convenience for the combination of trypsin. Additionally, the conformational simulation of the analogues processed with Chimera and Gromacs and further combination simulations between the peptides and trypsin conducted with HDOCK offered a potential opportunity for the natural trypsin inhibitory drug design. The truncated sequence, AH-798, may be a good replacement for the full-length peptide, and can be optimized via cyclization for further study. Full article
(This article belongs to the Special Issue Pharmaceutical Applications of Bioactive Peptides)
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32 pages, 5730 KiB  
Article
In Silico Selection and Evaluation of Pugnins with Antibacterial and Anticancer Activity Using Skin Transcriptome of Treefrog (Boana pugnax)
by Yamil Liscano, Laura Medina, Jose Oñate-Garzón, Fanny Gúzman, Monica Pickholz and Jean Paul Delgado
Pharmaceutics 2021, 13(4), 578; https://doi.org/10.3390/pharmaceutics13040578 - 18 Apr 2021
Cited by 3 | Viewed by 3006
Abstract
In order to combat bacterial and cancer resistance, we identified peptides (pugnins) with dual antibacterial l–anticancer activity from the Boana pugnax (B. pugnax) skin transcriptome through in silico analysis. Pugnins A and B were selected owing to their high similarity to [...] Read more.
In order to combat bacterial and cancer resistance, we identified peptides (pugnins) with dual antibacterial l–anticancer activity from the Boana pugnax (B. pugnax) skin transcriptome through in silico analysis. Pugnins A and B were selected owing to their high similarity to the DS4.3 peptide, which served as a template for their alignment to the B. pugnax transcriptome, as well as their function as part of a voltage-dependent potassium channel protein. The secondary peptide structure stability in aqueous medium was evaluated as well, and after interaction with the Escherichia coli (E. coli) membrane model using molecular dynamics. These pugnins were synthesized via solid-phase synthesis strategy and verified by Reverse phase high-performance liquid chromatography (RP-HPLC) and mass spectrometry. Subsequently, their alpha-helix structure was determined by circular dichroism, after which antibacterial tests were then performed to evaluate their antimicrobial activity. Cytotoxicity tests against cancer cells also showed selectivity of pugnin A toward breast cancer (MFC7) cells, and pugnin B toward prostate cancer (PC3) cells. Alternatively, flow cytometry revealed necrotic cell damage with a major cytotoxic effect on human keratinocytes (HaCaT) control cells. Therefore, the pugnins found in the transcriptome of B. pugnax present dual antibacterial–anticancer activity with reduced selectivity to normal eukaryotic cells. Full article
(This article belongs to the Special Issue Pharmaceutical Applications of Bioactive Peptides)
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24 pages, 3089 KiB  
Article
Antimicrobial Peptide against Mycobacterium Tuberculosis That Activates Autophagy Is an Effective Treatment for Tuberculosis
by Erika A. Peláez Coyotl, Jacqueline Barrios Palacios, Gabriel Muciño, Daniel Moreno-Blas, Miguel Costas, Teresa Montiel Montes, Christian Diener, Salvador Uribe-Carvajal, Lourdes Massieu, Susana Castro-Obregón, Octavio Ramos Espinosa, Dulce Mata Espinosa, Jorge Barrios-Payan, Juan Carlos León Contreras, Gerardo Corzo, Rogelio Hernández-Pando and Gabriel Del Rio
Pharmaceutics 2020, 12(11), 1071; https://doi.org/10.3390/pharmaceutics12111071 - 09 Nov 2020
Cited by 16 | Viewed by 3199
Abstract
Mycobacterium tuberculosis (MTB) is the principal cause of human tuberculosis (TB), which is a serious health problem worldwide. The development of innovative therapeutic modalities to treat TB is mainly due to the emergence of multi drug resistant (MDR) TB. Autophagy is a cell-host [...] Read more.
Mycobacterium tuberculosis (MTB) is the principal cause of human tuberculosis (TB), which is a serious health problem worldwide. The development of innovative therapeutic modalities to treat TB is mainly due to the emergence of multi drug resistant (MDR) TB. Autophagy is a cell-host defense process. Previous studies have reported that autophagy-activating agents eliminate intracellular MDR MTB. Thus, combining a direct antibiotic activity against circulating bacteria with autophagy activation to eliminate bacteria residing inside cells could treat MDR TB. We show that the synthetic peptide, IP-1 (KFLNRFWHWLQLKPGQPMY), induced autophagy in HEK293T cells and macrophages at a low dose (10 μM), while increasing the dose (50 μM) induced cell death; IP-1 induced the secretion of TNFα in macrophages and killed Mtb at a dose where macrophages are not killed by IP-1. Moreover, IP-1 showed significant therapeutic activity in a mice model of progressive pulmonary TB. In terms of the mechanism of action, IP-1 sequesters ATP in vitro and inside living cells. Thus, IP-1 is the first antimicrobial peptide that eliminates MDR MTB infection by combining four activities: reducing ATP levels, bactericidal activity, autophagy activation, and TNFα secretion. Full article
(This article belongs to the Special Issue Pharmaceutical Applications of Bioactive Peptides)
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Review

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17 pages, 2375 KiB  
Review
Peptide Allergen Immunotherapy: A New Perspective in Olive-Pollen Allergy
by David Calzada, Lucía Cremades-Jimeno, María López-Ramos and Blanca Cárdaba
Pharmaceutics 2021, 13(7), 1007; https://doi.org/10.3390/pharmaceutics13071007 - 02 Jul 2021
Cited by 12 | Viewed by 3120
Abstract
Allergic diseases are highly prevalent disorders, mainly in industrialized countries where they constitute a high global health problem. Allergy is defined as an immune response “shifted toward a type 2 inflammation” induced by the interaction between the antigen (allergen) and IgE antibodies bound [...] Read more.
Allergic diseases are highly prevalent disorders, mainly in industrialized countries where they constitute a high global health problem. Allergy is defined as an immune response “shifted toward a type 2 inflammation” induced by the interaction between the antigen (allergen) and IgE antibodies bound to mast cells and basophils that induce the release of inflammatory mediators that cause the clinical symptoms. Currently, allergen-specific immunotherapy (AIT) is the only treatment able to change the course of these diseases, modifying the type 2 inflammatory response by an allergenic tolerance, where the implication of T regulatory (Treg) cells is considered essential. The pollen of the olive tree is one of the most prevalent causes of respiratory allergic diseases in Mediterranean countries, inducing mainly nasal and conjunctival symptoms, although, in areas with a high antigenic load, olive-tree pollen may cause asthma exacerbation. Classically, olive-pollen allergy treatment has been based on specific immunotherapy using whole-olive pollen extracts. Despite extracts standardization, the effectiveness of this strategy varies widely, therefore there is a need for more effective AIT approaches. One of the most attractive is the use of synthetic peptides representing the B- or T-cell epitopes of the main allergens. This review summarizes experimental evidence of several T-cell epitopes derived from the Ole e 1 sequence to modulate the response to olive pollen in vitro, associated with several possible mechanisms that these peptides could be inducing, showing their usefulness as a safe preventive tool for these complex diseases. Full article
(This article belongs to the Special Issue Pharmaceutical Applications of Bioactive Peptides)
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