Spark is a powerful molecular modeling tool for the rapid virtual elaboration of scaffold ideas; either in scaffold hopping, merging, fragment growing or linking experiments. Cresset applied Spark to chemotypes bound to the active site of DPP-IV, resulting in a range of interesting and synthetically-feasible suggestions.
A customer had some existing active components that they wanted to link together in a different way. They already had a patent on one compound, but hoped to broaden their patent portfolio by re-linking the fragments in a different way and adding these new compounds to the patent. As they didn’t have an in-house computational chemistry team, they outsourced the work to Cresset Discovery Services.
The project consisted of an automatic exploration of alternative linking groups and possible chemistries. It was vital to find the right linking chemistry to result in compounds of the right shape to fit into the binding site. This would have been almost impossible to do without computational chemistry techniques.
Cresset Discovery Services used Spark to carry out searches for different linking groups. The project results are written up in the poster Scaffold Hopping into New DPP-IV Protease Inhibitors.
Example Spark™ calculation showing typical results using the protein and DPP IV inhibitor from the 3vjl crystal structure
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