Effective binding structures are an essential element of Structure-Based Drug Design. However, it can be challenging to obtain effective binding structures with peptide binders alone, such as cyclic peptides.
The following is the process that PepMetics™ Technology follows to generate hit compounds:
- Cyclic peptides often have the α-helix, β-turn or a similar structure;
- Assume a part of a cyclic peptide forms either an α-helix or β-turn and contributes to the interactions with a target;
- Synthesize PepMetics Molecules with three consecutive amino acids that shift one by one to mimic parts of the cyclic peptide sequence;
- Evaluate activities of PepMetics Molecules in order to obtain initial hit compounds. These hit compounds suggest possible homologous binding sequences;
- Predict the binding modes of the resulting hit compounds using an in silico docking simulation, thus confirming the Structure Activity Relationship (SAR);
- Based on the pharmacophore of the predicted binding modes, conduct further virtual screening and obtain true hits;