Therapeutic peptides: current applications and future directions

Abstract

Peptide drug development has made great progress in the last decade thanks to new production, modification, and analytic technologies. Peptides have been produced and modified using both chemical and biological methods, together with novel design and delivery strategies, which have helped to overcome the inherent drawbacks of peptides and have allowed the continued advancement of this field. A wide variety of natural and modified peptides have been obtained and studied, covering multiple therapeutic areas. This review summarizes the efforts and achievements in peptide drug discovery, production, and modification, and their current applications. We also discuss the value and challenges associated with future developments in therapeutic peptides.

A peptoid-based inhibitor of protein arginine methyltransferase 1 (PRMT1) induces apoptosis and autophagy in cancer cells

“…Peptides present a unique niche of pharmaceutical compounds that provide distinct physical and biochemical features to specifically bind to disease-related proteins. For example, peptides have been used as synthetic signaling molecules to regulate physiological functions and have also been used to disrupt protein–protein interactions ( 39 , 40 ). Furthermore, the ease of synthesis and low cost of production have made peptides favorable compounds as disease therapeutics.…”

In vitro Inhibition of HIV-1 by Cyclotide-Enriched Extracts of Viola tricolor

“…One unique class of therapeutic compounds are peptides which attained much attention over the course of the 20th century ( Lau and Dunn, 2018 ). Peptides are recognized for their high selectivity and efficacy and are relatively safe and well tolerated ( Mahlapuu et al, 2016 ; Wang et al, 2022 ). Peptide drugs now account for ∼7% of the total number of approved pharmaceuticals ( Al Musaimi et al, 2021 ) and this number is expected to increase in the near future because of the tremendous progresses made in peptide synthesis and purification ( Wang et al, 2022 ).…”

“…Making use of the natural evolution, a huge variety of already optimized peptides can be assessed ( Lazzaro et al, 2020 ; Atanasov et al, 2021 ). Peptides have a good efficacy compared to small molecules ( Wang et al, 2022 ) and a good safety profile because their degradation products are natural amino acids and they are generally less immunogenic than recombinant proteins or antibodies ( Mahlapuu et al, 2016 ). In contrary, first-generation antivirals have severe side effects due to pour specificity ( Mammari et al, 2021 ).…”

“…Cyclotides are expected to be broadly active due to their direct mode of action destabilizing lipid membranes ( Henriques and Craik, 2012 ; Henriques et al, 2012 ) which will most likely prevent resistance development ( Mahlapuu et al, 2016 ; Browne et al, 2020 ; Huan et al, 2020 ). Finally, peptides can be chemically modified and structure-activity-relationship studies can help to improve therapeutic features such as bioavailability, specificity and bioactivity ( Browne et al, 2020 ; Huan et al, 2020 ; Dijksteel et al, 2021 ; Wang et al, 2022 ). Typical AMPs have a low oral and systemic bioavailability due to enzymatic degradation ( Mahlapuu et al, 2016 ), but cyclotides have an exceptional resistance to degradation because of their unique topology ( Colgrave and Craik, 2004 ), making them a promising class of antivirals ( Lau and Dunn, 2018 ).…”

Solubility-aware protein binding peptide design using AlphaFold

“…More than 170 peptides have been in clinical development. As of 2021, there are 58 therapeutic peptides targeting PPIs in clinical stages, of which 13 are in Phase 1, 26 in Phase 2, 15 in Phase 3, and 4 have New Drug Applications pending and are close to approval [17,18].…”