Editorial: Peptidomimetics: Synthetic Tools for Drug Discovery and Development

The presented Research Topic includes papers and reviews, and it aims to provide an overview of the current state-of-the-art and recent advances within the field of peptidomimetics. Herlan et al. explore cyclic peptoid-peptide hybrids as a new class of highly efficient, versatile transporters into mitochondria selecting the fluorophore Rhodamine B as cargo. The review by Staśkiewicz and colleagues (doi.org/10.3389/fchem.2021.674705) provides an overview of the recent advancements in triazolyl-containing peptidomimetics. The authors highlight the most efficient synthetic methods for obtaining peptides containing 1, 2, 3-triazole moieties and report the promising activity of some triazolyl peptidomimetics as inhibitors of enzymes or as agents against cancer, viruses, bacteria, or fungi. The review by Olson et al. (doi.org/10.3389/fchem.2021.671483) highlights the sources and strategies that have been used to identify both peptide and peptidomimetic-derived allosteric modulators of GPCRs. It provides an overview of the approaches used to convert peptide leads into peptidomimetics. A critical discussion on the potential opportunities and challenges regarding the future development of peptidomimetics in the area of allosteric modulator drug discovery is also provided. Geranurimi et al.( doi.org/10.3389/fchem.2020.610431) describe the synthesis and biological evaluation of a series of modified peptides, which are analogs of the all D-amino acid heptapeptide rytvela, previously reported as an allosteric IL-1R modulator that conserves NF-κB signalling while inhibiting other IL-1-activated pathways. Afonin et al. (doi.org/10.3389/fchem.2021.688446) report the synthesis, biophysical, and in vivo studies of aknown AMP, explored using a 3-hydroxychromone-derived fluorescent amino acid in place of the original aromatic amino acids. They evaluate the effects of such modifications in terms of structure-activity relationship and demonstrate that the use of this kind of peptidomimetics is an efficient strategy enabling in vivo peptide-cell and peptide-organism interactions monitoring. In this issue, Hu et al. (doi.org/10.3389/fchem.2020.616147) design and synthesize a series of all-hydrocarbon stapled analogs of antimicrobial peptide A4K14-Citropin 1.1. Among the synthetic analogs, two stapled peptides display improved protease stability and increased antitumor activity compared to the flexible linear counterpart.