PEMfinder® Library
PEMfinder® is a proprietary, diverse library composed of > 20’000 Protein Epitope Mimetics (PEM) incorporating pharmacophore design inputs of several target classes. Using a ligand-based design approach, Polyphor designed and synthesized a general library 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). The following target/ligand-based structural inputs were integrated into the PEMfinder® design:
- Natural peptide sequences
- Phage peptides
- Key peptide motifs (RGD, WKY, etc.)
- Key pharmacophores (turn-like; helical)
- Site-directed mutagenesis data (epitope mapping)
- X-ray/NMR structural analysis of ligands and their receptors
Peptide sequences derived from phage peptides, peptidic natural products, natural peptide and protein ligands of GPCRs and peptide hormones are an especially rich source for PEM design. 2D- and 3D pharmacophores of peptide ligands for the following target classes have been analyzed and used for the PEMfinder® library design:
- GPCR ligands (e.g. urotensins, vasopressins, bradykinins, neurokinins, endothelins, somatostatins, chemokines)
- Ion channel blockers (e.g. toxins from conii, spiders, snakes sea anemonae, tarantulae)
- Ligands of extracellular growth factor receptors (e.g. VEGF, PDGF)
- Transcription factors/activators (e.g. STAT-6/NCoA-1, P53/HDM2)
- Natural peptidic protease inhibitors
Ligand-based 2D- and 3D- pharmacophore design hypotheses obtained from various sources mentioned above were analyzed and translated into PEMfinder® library design.
