Special Issue "Peptides of Natural Origins as Leads for Drug Discovery: From Native Structures to Peptidomimetics, Peptide-Conjugates, and Peptide-Nanoparticles"
Deadline for manuscript submissions: closed (30 April 2021).
2. CIRI Health Sciences and Technologies (HST), Bologna, Italy
Interests: peptides; peptidomimetics; nitrogen heterocycles; conformational analysis; docking; opioids; integrins; addiction; cancer; biomaterials; diagnostic devices; inflammation
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2. Department of Organic Chemistry, University of Barcelona, CIBER-BBN, Barcelona, Spain
Interests: antimicrobial peptides; solid-phase chemistry; combinatorial chemistry; drug delivery systems; peptide drug conjugates; orthogonal chemistry; drug discovery; biomaterials
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Despite of recent scientific and technological advances, drug R&D productivity continues its exponential decline, dramatically depicted by the “Eroom’s Law”. This negative trend has encouraged pharmaceutical companies to reconsider bioactive natural peptides as valuable leads for drug discovery. After an initial enthusiasm until the 80s (human insulin was introduced in 1982 as the first recombinant drug), peptides almost sank into oblivion by the end of the 20th century. The reasons for this largely stem from the prejudice that the cons greatly outweigh the pros. Native peptides may suffer from poor metabolic stability, scarce to null ability to penetrate across biological barriers, and rapid clearance. Besides, inefficient and expensive manufacturing hampered the production of large amounts of peptides. Nevertheless, the past two decades have seen a significant increase in the investments in peptide drug discovery. The case of enfuvirtide demonstrated that producing a 36-residue peptide on a ton-scale per year could be cost effective. Additionally, the recourse to alternative routes of administration (e.g., pulmonary, nasal, intradermal), to the peptidomimetic strategy, and the conjugation to carriers or nanoparticles, allowed the bioavailability of native structures to be improved. Therapeutic peptides offer several advantages over small molecules—that is, greater efficacy and specificity, reduced toxicity, and reduced accumulation. Compared with proteins and antibodies, peptides have lower manufacturing costs and higher activity per unit mass, are less immunogenic, can be stored for longer periods, and have the potential to penetrate into tissues owing to their smaller size. Finally, peptides require a shorter time to reach the market, and are less problematic in terms of royalty stack because of a simpler intellectual property.
The global peptide therapeutics market was valued at USD 21.5 billion in 2016, and is expected to grow at a rate of 9.4% per year, reaching USD 48.04 billion by 2025. Presently, more than 60 peptide therapeutics are marketed worldwide, another ca. 170 are in various stages of clinical development, and more than 200 others are at preclinical stages. The predominant therapeutic areas are in metabolic diseases and oncology, followed by infections, cardiovascular, respiratory, renal, and gastro-intestinal disorders, pain, CNS, and dermatology. The year 2017 was exceptional for peptide and peptidomimetic drugs, with six approved in comparison with one in 2016: angiotensin II (control of blood pressure), etelcalcetide (secondary hyperparathyroidism), plecanatide (chronic idiopathic constipation), abaloparatide (osteoporosis), semaglutide (type 2 diabetes mellitus), and macimorelin (GH deficiency).
In this Issue, we intend to present the recent trends in peptide drug discovery, from the naturally occurring peptides to the peptidomimetics, from therapeutic applications to the new opportunities enabled by the conjugation with biomaterials and nanotechnology.
Prof. Dr. Luca Gentilucci
Prof. Dr. Fernando Albericio
Manuscript Submission Information
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