Circle is taking a new approach to the development of macrocylic peptide therapeuticsthat is based on the pioneering work of its founders to understand and computationally predict drug-like properties of macrocycles. Circle is advancing this understanding to design novel, inherently permeable macrocyclic peptide drug candidates against Circle’s internal targets and those of our collaboration partners.
Our workflow includes the use of proprietary algorithms to design large, conformationally diverse, virtual libraries of cell permeable macrocyclic scaffolds that incorporate natural and non-natural backbone components. We deploy these virtual scaffold libraries in subsequent design steps that include the incorporation of functional side chains selected for both target binding and maintenance of permeability. Candidate compounds are synthesized and tested for both permeability and target affinity and the results are used to inform subsequent design cycles.