Peptide Synthesis and Drug Development: Exploring Progress and Potential, 2nd Edition

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

Deadline for manuscript submissions: 31 July 2026 | Viewed by 448

Special Issue Editors


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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
3. Orthogonal Peptides Limited, London SW7 2AZ, UK
Interests: peptide synthesis; separation; purification and greening; drug development
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Bachem AG, Hauptstrasse 144, 4416 Bubendorf, Switzerland
Interests: peptides; TIDES; drug discovery; medicinal chemistry; CMC; DMPK; marketed peptides
Special Issues, Collections and Topics in MDPI journals

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 120 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. Vera D'Aloisio
Guest Editors

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Keywords

  • peptides
  • enzymatic degradation
  • drug discovery
  • formulation
  • druggability

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Published Papers (1 paper)

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Review

29 pages, 2543 KB  
Review
Pharmaceutical Peptides: From Synthesis and Mechanistic Pharmacology to Future Biologic Therapeutics
by Muhammad Yaseen Khan, Touseef Nawaz, Muhammad Sajid Hamid Akash and Adnan Amin
Pharmaceuticals 2026, 19(6), 811; https://doi.org/10.3390/ph19060811 - 22 May 2026
Viewed by 119
Abstract
Peptide therapeutics have emerged as a versatile class of biomolecules bridging the gap between small-molecule drugs and large biologics. Advantages of such molecules include high target specificity, potent bioactivity and reduced off-target toxicity. Despite these, broader clinical translation remains constrained by inherent limitations [...] Read more.
Peptide therapeutics have emerged as a versatile class of biomolecules bridging the gap between small-molecule drugs and large biologics. Advantages of such molecules include high target specificity, potent bioactivity and reduced off-target toxicity. Despite these, broader clinical translation remains constrained by inherent limitations like poor metabolic stability, rapid renal clearance, limited membrane permeability and scalable synthesis. This review aims to systematically integrate advances in peptide science across natural discovery, synthetic methodologies, structural engineering, and translational delivery systems, while identifying critical research gaps hindering clinical adoption. We highlight diverse natural sources of bioactive peptides, including plant- (lunasin), animal- (Val-Pro-Pro (VPP) and Ile-Pro-Pro (IPP)), microbial- (nisin and cyclosporine), marine- (dolastatins) and venom-derived (chlorotoxin and ω-conotoxin MVIIA (ziconotide)) agents. Advances in solid-phase peptide synthesis (SPPS), green chemistry, and catalytic strategies are discussed alongside emerging in silico approaches, including artificial intelligence-driven sequence design and molecular modeling. Structural modifications such as cyclization, hydrocarbon stapling, PEGylation, and lipidation are critically evaluated for their role in enhancing pharmacokinetic and pharmacodynamic properties. Furthermore, nanoformulation strategies, including self-assembling peptides and cell-penetrating systems, are examined for their potential to overcome biological barriers. Importantly, this review identifies key unresolved challenges, including the lack of predictive models for peptide delivery systems, safety concerns associated with long-term modifications, and limited in vivo validation of naturally derived peptides. Addressing these gaps through integrated computational and experimental approaches will be essential for advancing next-generation peptide therapeutics. Collectively, this work provides a comprehensive framework for the rational design and translation of peptide-based precision medicines. Full article
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