Technology will exploit chemical space in peptide libraries to determine target-binding conformation.
Isogenica, Biolauncher, and Cresset have received a grant from the U.K.’s Technology Strategy Board to fund a £1 million project focused on developing a cost-effective, rapid, and highly scalable small molecule drug discovery platform. The goal is to develop an integrated platform for the identification of small molecule drugs against intracellular, extracellular, and membrane-bound targets, using peptides identified from huge libraries as structural templates. The components of the overall platform have been developed by the three partners, and already used widely as individual drug disocvery tools.
The approach essentially uses peptide libraries as a starting point for the subsequent design of small molecule drugs. The process starts with the selection of diverse peptides from Isogenica’s libraries that bind to a biological target. The binding peptides are then analyzed using a structural bioinformatics technology developed by Biolauncher to determine the active conformation. The resulting 3-D template is then used to generate a field-based pharmacophore that Cresset can use to identify small molecule starting points for drug design. “Coupling Isogenica’s massive screening libraries with Cresset’s small molecule bioisostere discovery tools offer the possibility to bridge biologics directly into small molecule chemistry,” explains Kevin Mathews, Isogenica CEO.
The firms claim that working with diverse populations of binding peptides will facilitate the determination of which residues are actively involved in target binding. “The diversity of the chemical libraries in corporate collections can be quite limited and so the percentage of chemical space represented is small,” comments BioLauncher’s Rowan Gardner, who is heading the collaboration’s business development activity.
“Isogenica’s peptide libraries are designed to be structurally very diverse and sample a much greater volume of chemical space. Also, in addition to acting as a structural template, there is a high probability of finding binding peptides that have immediate utility as reagents for probing the target biology and supporting the drug development process.”