Oxadiazole grafts in peptide macrocycles

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In 2016, we discovered a macrocyclization reaction that rapidly converts readily accessible linear peptides into macrocycles with well-defined conformation. (N-isocyanimino)triphenylphosphorane, instrumental to this reaction, was later named "Pinc" to identify the presence of phosphonium and isocyanide functionalities. This work was published in Nature Chemistry and was subsequently covered by The Chemical & Engineering News and Science. On the heels of this discovery, we applied for a patent application (PCT/CA2016/000234) that described the method of cyclizing peptides with simultaneous incorporation of an oxadiazole graft into the resulting macrocyclic structures. We also received market assessment funding from NSERC allowing us to retain the services of Adventus Research who carried out a thorough market assessment study (see the 85-page report attached).The present I2I application considers the main messages from that report and focuses on two applications that will further de-risk our technology now that it is sufficiently mature. The first one is to develop an approach to the synthesis of improved derivatives of Pinc. The second one deals with peptide macrocycles produced using Pinc in order to further validate our approach to novel composition of matter. To move forward, we will engage in collaborative activity to produce Pinc (together with MilliporeSigma), initiate translational studies aimed at the use of Pinc toward heterocycle synthesis (together with Apotex), and evaluate the potential of Pinc-derived macrocycles in drug discovery (together with Encycle and Merck).