Tony, I’ve only come across a couple of potentially relevant items.
Firstly, in an interview given in 2012, Patrick Reid (CEO of Peptidream) said that PeptiDream’s technology can make cell-permeable macrocycles of 800–2,000 Da. He expressed the view that hydrophobicity and the 3D structure of the macrocycle seemed to be more important than size in determining cell permeability.
At that time, he said that about half of the company’s targets were extracellular and the other half intracellular. The company’s most advanced program against an intracellular target at the time was an undisclosed proteinprotein interaction being pursued as part of a pharma collaboration.
In what he described as a “major direction” for the company, he said they were in the process of designing new libraries with different scaffolds and developing new selection techniques, with an eye toward increasing cell permeability.
In another paper from Peptidream which was published last year, its scientists (including Reid) say that using PDPS technology, they have generally been able to deliver potent hits for about 90% of the protein targets they have tested to date, even for targets widely deemed “undruggable”.
They concede that cell permeability remains one of the most challenging aspects of peptide therapeutic development and that most peptides and constrained peptides to date are not suitable for intercellular targets.
They also reveal that they have now extended the PDPS technology for constrained peptide discovery to include the discovery and development of peptide-drug conjugates (PDCs). They state that “While the newer field of PDCs is just beginning to take off, there are several reasons to expect the clinical use of PDCs to compare favourably to antibody-drug conjugates( ADCs)".
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