Hit Identification

Polyphor's proprietary complementary discovery tools:

  • PEMfinder® Library
  • PEMphage® Display
  • MacroFinder® Library

 

PEMfinder® Library

PEMfinder® is a proprietary, diverse library composed of > 30’000 Protein Epitope Mimetics (PEM) incorporating pharmacophore design inputs of several target classes. Using a ligand-based design approach, Polyphor has designed and synthesized a general library of PEMs with a high propensity to hit G protein-coupled receptors (GPCRs) with large ligand-binding sites, ion channels and other targets involving protein-protein interactions (PPIs). For more details about the PEMfinder® Library please view PDF document.

PEMphage® display

PEMphage® display constitutes an important extension of PEM Technology. It forms a unique structural link between the huge combinatorial potential of biological synthesis and the power of chemical synthesis of PEM Technology.

Polyphor routinely uses its proprietary PEMphage® display technology to support the hit identification process wherever necessary and possible. Phage peptides in ß-hairpin conformation provide the most useful sequence information for the design of PEM molecules. The ß-hairpin conformation of the phage peptides is induced by two elements: A disulfide bridge and sequences of amino acids with a tendency to pair known as PEM boxes. Once active phage peptides have been identified, their sequence can be directly transferred into PEM molecules. Polyphor’s PEMphage® library, which contains about 109 phage sequences, together with commercially available phage libraries have been successfully used in several hit identification programs involving recombinant proteins and whole cells. 

MacroFinder® Library

MacroFinder® screening library characteristics

  • Variable ring size (12-30, typically 12-18) with a molecular weight of 400-800 Dalton
  • Semi-rigid backbone conformations induced by built-in structural constraints
  • High degree of conformational fine tuning possible through variation of ring size and stereochemistry of modular building blocks
  • Low energy conformations of many scaffolds determined by 2D NMR
  • Single purified and untagged molecules amenable to all screening formats including cellular, pathway or phenotypical screening methodologies
  • Modular design allows efficient introduction of several privileged structural motifs
  • MacroFinder® molecules show natural product-like structural complexity and exhibit small-molecule-like ADMET properties, in particular excellent cell penetration and oral bioavailability have been demonstrated
  • Efficient optimization due to established automated parallel synthesis methodologies (mixed solid and solution phase synthesis) in array formats of 400-600 cpds 
  • Systematic design and production of a diverse range of macrocyclic compounds. Currently, >15’000 MacroFinder® compounds are available for screening drug discovery collaborations

 

Targets for MacroFinder®

MacroFinder® molecules are ideally suited to tackle difficult intracellular targets. In addition MacroFinder® compounds can be readily optimized to achieve oral bioavailability if required.