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Pharmaceuticals
Special Issues
Peptide Synthesis and Drug Development: Exploring Progress and Potential
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Peptide Synthesis and Drug Development: Exploring Progress and Potential

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Biopharmaceuticals".

Deadline for manuscript submissions: 25 November 2025 | Viewed by 4650

Special Issue Editors

Dr. Othman Al Musaimi

E-Mail Website
Guest Editor
1. School of Pharmacy, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne NE1 7RU, UK
2. Department of Chemical Engineering, Imperial College London, London SW7 AZ, UK
Interests: peptide synthesis; separation; purification and greening; drug development
Special Issues, Collections and Topics in MDPI journals
Dr. Da’san M.M. Jaradat

E-Mail Website
Guest Editor
1. Department of Chemistry, Faculty of Science, Al-Balqa Applied University, P.O. Box 206, Al-Salt 19117, Jordan
2. Helmholtz-Zentrum Berlin für Materialien und Energie (HZB), Berlin, Germany
Interests: solid-phase peptide synthesis; drug development
Dr. Vera D'Aloisio

E-Mail Website
Guest Editor
Bachem AG, Hauptstrasse 144, 4416 Bubendorf, Switzerland
Interests: peptides; TIDES; drug discovery; medicinal chemistry; CMC; DMPK; marketed peptides

Special Issue Information

Dear Colleagues,

Peptides are becoming increasingly important in a variety of fields such as drug development, immunology, sensing, and biomaterials. Because of their significant binding footprint with therapeutic targets, peptides are regarded as superior to their small-molecule counterparts. On the other hand, they encounter stability challenges due to enzymatic degradation. Ongoing efforts to harmonise interdisciplinary fields have been instrumental in improving the pharmacokinetic and pharmacodynamic profiles of peptides.

Out of roughly 102 approved peptides, since 1923, a mere 11 have been found to be suitable for oral administration. This represents only 3.4% of all approvals. While traditional chemical methods have been employed to improve peptide stability, there has been a lack of exploration into innovative chemistries.

For this Special Issue, we invite authors to present and/or review novel strategies for addressing this challenge. This includes introducing new synthetic methodologies and formulation strategies. Additionally, computational studies aimed at achieving the same objective are also encouraged.

Dr. Othman Al Musaimi
Dr. Da’san M.M. Jaradat
Dr. Vera D’Aloisio
Guest Editors

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. Pharmaceuticals 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

  • peptides
  • enzymatic degradation
  • drug discovery
  • formulation
  • draggability

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Published Papers (3 papers)

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Research

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24 pages, 6370 KiB  
Article
Influence of Peptide Conjugation Sites on Lunatin–Alumina Nanoparticles: Implications for Membrane Interaction and Antimicrobial Activity
by Carolina Silva Ferreira, Lívia Mara Fontes Costa, Lúcio Otávio Nunes, Kelton Rodrigues de Souza, Giovanna Paula Araújo, Evgeniy S. Salnikov, Kelly Cristina Kato, Helen Rodrigues Martins, Adriano Monteiro de Castro Pimenta, Jarbas Magalhães Resende, Burkhard Bechinger and Rodrigo Moreira Verly
Pharmaceuticals 2025, 18(7), 952; https://doi.org/10.3390/ph18070952 - 24 Jun 2025
Viewed by 43
Abstract
Background/Objectives: The increasing prevalence of multidrug-resistant bacteria presents a major global health challenge, prompting a search for innovative antimicrobial strategies. This study aimed to develop and evaluate a novel nanobiostructure combining alumina nanoparticles (NPs) with the antimicrobial peptide lunatin-1 (Lun-1), forming peptide-functionalized nanofilaments. [...] Read more.
Background/Objectives: The increasing prevalence of multidrug-resistant bacteria presents a major global health challenge, prompting a search for innovative antimicrobial strategies. This study aimed to develop and evaluate a novel nanobiostructure combining alumina nanoparticles (NPs) with the antimicrobial peptide lunatin-1 (Lun-1), forming peptide-functionalized nanofilaments. The main objective was to investigate how the site of peptide functionalization (C-terminal vs. N-terminal) affects membrane interactions and antibacterial activity. Methods: NP–peptide conjugates were synthesized via covalent bonding between lun-1 and alumina NP and characterized using transmission electron microscopy (TEM), X-ray diffraction (XRD), zeta potential analysis, dynamic light scattering (DLS), Fourier-transform infrared (FTIR), and solid-state 13C NMR. Antibacterial activities were assessed against different Gram-positive and Gram-negative strains. Biophysical analyses, including circular dichroism (CD), isothermal titration calorimetry (ITC), differential scanning calorimetry (DSC), and solid-state 2H NMR, were employed to evaluate peptide–membrane interactions in the presence of membrane-mimetic vesicles composed of POPC:POPG (3:1) and DMPC:DMPG (3:1). Results: Characterization confirmed the successful formation of NP–peptide nanofilaments. Functionalization at the N-terminal significantly influenced both antibacterial activity and peptide conformation compared to C-terminal attachment. Biophysical data demonstrated stronger membrane interaction and greater membrane disruption when lun-1 was conjugated at the N-terminal. Conclusions: The site of peptide conjugation plays a crucial role in modulating the biological and biophysical properties of NP–lunatin-1 conjugates. C-terminal attachment of lunatin-1 retains both membrane interaction and antibacterial efficacy, making it a promising strategy for the design of peptide-based nanotherapeutics targeting resistant pathogens. Full article
(This article belongs to the Special Issue Peptide Synthesis and Drug Development: Exploring Progress and Potential)
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Review

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24 pages, 2492 KiB  
Review
Antioxidant Peptides Derived from Woody Oil Resources: Mechanisms of Redox Protection and Emerging Therapeutic Opportunities
by Jia Tu, Jie Peng, Li Wen, Changzhu Li, Zhihong Xiao, Ying Wu, Zhou Xu, Yuxi Hu, Yan Zhong, Yongjun Miao, Jingjing Xiao and Sisi Liu
Pharmaceuticals 2025, 18(6), 842; https://doi.org/10.3390/ph18060842 - 4 Jun 2025
Viewed by 372
Abstract
Antioxidant peptides derived from woody oil resource by-products exhibit strong free radical scavenging abilities and offer potential applications in functional foods, nutraceuticals, and cosmetics. This review summarizes the latest advances in preparation technologies, including enzymatic hydrolysis, microbial fermentation, chemical synthesis, recombinant expression, and [...] Read more.
Antioxidant peptides derived from woody oil resource by-products exhibit strong free radical scavenging abilities and offer potential applications in functional foods, nutraceuticals, and cosmetics. This review summarizes the latest advances in preparation technologies, including enzymatic hydrolysis, microbial fermentation, chemical synthesis, recombinant expression, and molecular imprinting, each with distinct advantages in yield, selectivity, and scalability. The structure–activity relationships of antioxidant peptides are explored with respect to amino acid composition, molecular weight, and 3D conformation, which collectively determine their bioactivity and stability. Additionally, emerging delivery systems—such as nanoliposomes, microencapsulation, and cell-penetrating peptides—are discussed for their role in enhancing peptide stability, absorption, and targeted release. Mechanistic studies reveal that antioxidant peptides from woody oil resources act through network pharmacology, engaging core signaling pathways, including Nrf2/ARE, PI3K/Akt, AMPK, and JAK/STAT, to regulate oxidative stress, mitochondrial health, and inflammation. Preliminary safety data from in vitro, animal, and early clinical studies suggest low toxicity and favorable tolerability. The integration of omics technologies, molecular docking, and bioinformatics is accelerating the mechanism-driven design and functional validation of peptides. In conclusion, antioxidant peptides derived from woody oil resources represent a sustainable, multifunctional, and scalable solution for improving human health and promoting a circular bioeconomy. Future research should focus on structural optimization, delivery enhancement, and clinical validation to facilitate their industrial translation. Full article
(This article belongs to the Special Issue Peptide Synthesis and Drug Development: Exploring Progress and Potential)
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38 pages, 4414 KiB  
Review
Recent Advances in Peptide-Loaded PLGA Nanocarriers for Drug Delivery and Regenerative Medicine
by Hossein Omidian, Renae L. Wilson and Ana M. Castejon
Pharmaceuticals 2025, 18(1), 127; https://doi.org/10.3390/ph18010127 - 18 Jan 2025
Cited by 4 | Viewed by 3160
Abstract
Peptide-loaded poly(lactide-co-glycolide) (PLGA) nanocarriers represent a transformative approach to addressing the challenges of peptide-based therapies. These systems offer solutions to peptide instability, enzymatic degradation, and limited bioavailability by providing controlled release, targeted delivery, and improved stability. The versatility of PLGA nanocarriers extends across [...] Read more.
Peptide-loaded poly(lactide-co-glycolide) (PLGA) nanocarriers represent a transformative approach to addressing the challenges of peptide-based therapies. These systems offer solutions to peptide instability, enzymatic degradation, and limited bioavailability by providing controlled release, targeted delivery, and improved stability. The versatility of PLGA nanocarriers extends across therapeutic domains, including cancer therapy, neurodegenerative diseases, vaccine development, and regenerative medicine. Innovations in polymer chemistry, surface functionalization, and advanced manufacturing techniques, such as microfluidics and electrospraying, have further enhanced the efficacy and scalability of these systems. This review highlights the key physicochemical properties, preparation strategies, and proven benefits of peptide-loaded PLGA systems, emphasizing their role in sustained drug release, immune activation, and tissue regeneration. Despite remarkable progress, challenges such as production scalability, cost, and regulatory hurdles remain. Full article
(This article belongs to the Special Issue Peptide Synthesis and Drug Development: Exploring Progress and Potential)
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