Therapeutics is developing these peptides as standalone therapeutics or as a potential targeting platform . ²³ Similar to this technology , the Pentelute laboratory has been also exploiting macrocylisation with thioether chemistry through reactions of Cys residues with perfluoroarene . The resulting peptides are stabilised and have enhanced cell-penetrating properties for delivery across the blood-brain barrier . ²⁴ Recently , they have made bicyclic perfluoroarylpeptides containing cell penetrating motifs for the delivery of antisense oligonucleotides . ²⁵ Another company developing macrocyclic peptides for therapeutic indications is Peptidream , located in Japan . This company , which was co-founded by Dr Hiroaki Suga , has licensed technology developed by him at the University of Tokyo is using flexisyme technology for loading tRNAs with novel amino acids . ²⁶ These are used in their proprietary peptide discovery translation system coupled with macrocyclisation and modification to develop peptide leads rapidly . A recent review from the Suga lab summarises many of these

Figure 3 – Balixafortide constraints

techniques . ²⁷ Peptidream uses many constraint technologies to develop peptides for large pharmaceutical partners , including Novartis , Merck , GSK , Shionogi and many others .

Conclusions

Hopefully , this mini-review will provide those interested in the developing area of therapeutic macrocyclic peptides with a good starting point to gain some perspective . It is by no means a comprehensive summary of the field , however . An excellent current review of this topic from Jing and Jin can provide a much deeper dive into this technology . ²⁸ •

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