Protein kinases play a crucial role in signal transduction and also in cellular proliferation, differentiation and various regulatory mechanisms
Peakdale Molecular and BioLeap have entered into a collaboration to design and synthesise highly focused kinase libraries for drug discovery, with the initial project targeting the c-Abl Tyrosine Kinase.
By combining BioLeap's leading edge computational fragment-based design capabilities with Peakdale's innovative chemistry expertise, the collaboration is set to produce drug-ike compounds that produce high quality, patentable leads for the pharmaceutical industry, the comapnies say.
The new libraries will focus on tyrosine kinase targets and will expand the current Peakexplorer collections that comprise over 5000 novel GPCR screening compounds.
Protein kinases play a crucial role in signal transduction and also in cellular proliferation, differentiation and various regulatory mechanisms.
The inhibition of growth-related kinases, especially tyrosine kinases such as c-Abl Tyrosine Kinase, has the potential to provide new therapies for diseases such as cancer.
Of particular interest to Peakdale's chemists is BioLeap's proprietary technology that rapidly calculates the free energies of interaction between small molecular fragments and biomolecular structures, displaying the distribution and orientation of these fragments.
One immediate benefit of this technology is the prediction of sites where tightly bound waters can be identified that cannot be seen in crystallography due to their high entropy.
This information provides a unique insight into how small molecules bind into key protein binding sites that cannot be achieved from the static crystal structure alone, or from methods that can only measure the enthalpic properties of binding.
In addition to lead discovery, the quantitative free-energy based analysis of protein-ligand interactions adds significant value to the lead optimisation process.
This information will allow Peakdale's chemists to design novel compounds with better drug-like properties than existing compounds.
Commenting on the collaboration, BioLeap's Gerry Evans noted: "Peakdale is known for its ability to create novel chemical structures for pharmaceutical research and this fits very well with BioLeap's expertise in providing unique binding information on key biological targets".
Ray Fisher, Peakdale commercial director, added: "This collaboration is about taking existing compounds, that are known to bind to the c-Abl Tyrosine kinase, and improving their drug-like qualities through the use of x-ray crystallography, computational fragment-based design and innovative chemistry.
"We will also benefit from BioLeap's expertise in kinase targets.
"BioLeap's technology will also be used to provide an in silico fragment approach to ligand design by identifying parts of the protein target that could bind to small fragments.
"In turn Peakdale's chemists are skilled at assimilating this data and converting this knowledge into new designs for screening compound libraries."
