Our technology will bring new medicines for diseases of unmet clinical need
A range of sizes of GyrocycleTM macrocyclic peptides can be generated, and a variable number of heterocycle rings incorporated into the product. The final macrocycle may contain 0-6 heterocycles.
Many different chemical moieties can be accommodated by our technology as shown in Fig. 1.
Other macrocycles have been made incorporating residues with chemical groups suitable for further chemical modification.
Variations around a hit molecule can be made by using different enzymes and reaction schemes, including further tailoring by oxidation of the heterocycles (Thz, Oxz) and decoration with prenyl groups. Using this protocol a single linear peptide substrate will yield a discrete set of modified cyclic peptides (5 in the example shown in Fig. 2), each with a distinct conformation, and a range of target binding and physicochemical properties.
The heterocycles within the backbone of our compounds force the adoption of predictable compact conformations, as shown in Figs. 3 & 4. These are ideal for matching pharmacophores.
The advantages of GyrocycleTM drugs include:
1. Modulation of challenging targets such as protein-protein interactions
2. Ability to cross biological membranes and reach intracellular targets
3. Stability to metabolism
4. Improved target affinity/specificity
5. Potential for oral bioavailability
6. Access to novel patentable chemical space
Benefits of the Technology