Vorherr, Thomas (2018) Peptide Therapeutics. Bioorganic and medicinal chemistry.

Abstract

Contributions highlighted in this Symposium-in-Print provide a snapshot of topics relevant for the various aspects of peptide therapeutics, and by no means, this assembly of manuscripts can achieve complete coverage of the field. Nevertheless, this collection clearly indicates the various opportunities for peptides in drug discovery. Similarly, this is exemplified in the first contribution of M. Dunn and J. Lau regarding the trends for the therapeutic peptide landscape. The market for peptide therapeutics experiences a strong and steady growth across a wide range of disease areas. Thus, companies investing in this area are supposed to profit, if indications and projects are chosen wisely.
In the first instance, the sequence of articles follows more or less the drug discovery track. In most cases, projects start with more theoretical considerations. Artificial intelligence and in-silico design, in particular to permit structure and property prediction, are becoming more and more important during the early drug discovery process and even up to the analyses of clinical results. The contribution on machine-learning is regarded as a showcase in this context. As a next step, dependent on the project, hits may be generated from natural products (animals, humans, plants etc), synthetic libraries, and/or by display technologies. In particular, the latter two topics have not really been covered separately, however excellent reviews are available.1, 2
Optimization of hits is often required to manipulate the properties, e.g. permeability and stability. For this reason, an overview of the peptide chemical toolbox indicates the various options. Cyclic peptides and modifications thereof to achieve membrane penetration have received special attention, which bridge the gap to classical medicinal chemistry. In addition, particular sequence motifs and scaffolds able to be taken up into cells, so called cell penetrating peptides are of interest. By contrast to most of the publications in this area, the corresponding summary by R. Brock provides a realistic picture what can be expected. Furthermore, targeting cells, organs, microbes (e.g. with Teixobactin), or tumors represents another route to innovative medicines based on peptides.
The combination of medical imaging with immediate next steps for therapy represents another interesting approach for peptides. Following a description on modifications with respect to insulin-like peptides, articles exemplifying the use for application as vaccines in the context of cancer immunotherapy, as antibiotics, to treat CNS-diseases, to overcome GI-disorders, and for the treatment of diabetes and obesity clearly show the impact of peptides across disease areas.
The final series of mini-reviews nicely complements this collection by offering insights into options for half-life extension, considerations regarding formulation and adaptations required for manufacturing the latest generation of peptide APIs. For more chemical options regarding half-life extension, the recent review by K. Jensen is recommended.3
I would like to express my gratitude to the authors regarding their valuable contributions, which helped to achieve an excellent coverage of the field of Peptide Therapeutics. In addition, I am grateful to Prof. Herbert Waldmann, who provided me with the opportunity to serve as a Guest Editor, and Birgit Apprecht for her expert help to assemble this SiP issue.
References

1 B. P. Gray, K. Brown, Combinatorial peptide libraries: mining for cell-binding peptides, Chem. Rev. 114 (2014) 1020-1081

2 N. K. Bashiruddin, H. Suga, Construction and screening of vast libraries of natural product-like macrocyclic peptides using in vitro display technologies, Curr. Opin. Chem. Biol. 24 (2015) 131-138

3 S. B. van Witteloostuijn, S. L. Pedersen, K. J. Jensen, Half-Life Extension of Biopharmaceuticals using Chemical Methods: Alternatives to PEGylation, ChemMedChem 11 (2016) 2474-2495

Item Type:	Article
Date Deposited:	03 Jul 2018 00:45
Last Modified:	03 Jul 2018 00:45
URI:	https://oak.novartis.com/id/eprint/34736