Thermo Fisher Scientific has announced that its Maybridge Ro3 Diversity Fragment Library has helped researchers validate a drug-discovery technique that targets key protein receptors.
David Myszka, founder of Biosensor Tools and director of the Center for Biomolecular Interaction Analysis at the University of Utah, used surface plasmon resonance (SPR) to screen small molecules/fragments in the Maybridge Ro3 collection against stabilised G-Protein Coupled Receptors (GPCRs) provided by Heptares Therapeutics1.
Several new classes of compounds were identified from the Ro3 library, which is accelerating drug discovery efforts around these receptors.
Dr Myszka's study demonstrated for the first time that fragment screening by SPR is an effective approach, as it utilises the sensor surface to purify and concentrate solubilised tagged GPCRs, then to characterise their binding activities with the fragments.
Dr Myszka and Rebecca Rich, a research scientist in Dr Myszka's group, recently presented their work 'Fragment Screening against Membrane Receptors using SPR,' at the Fragment-Based Lead Discovery Conference in Philadelphia and at the Developments in Protein Interaction Analysis symposium in Barcelona, Spain.
They attributed their success partly to the integrity of the Maybridge Ro3 Fragments, stating that the library was well-behaved in terms of high solubility and displayed minimal nonspecific binding or so-called promiscuous binders.
According to the scientists, the library's structural diversity allowed them to span a lot of chemical space, helping them to identify subsets of novel compounds that targeted two GPCRs.
Thermo Fisher Scientific added: 'The guaranteed aqueous solubility of Maybridge Ro3 Fragments is not only key from a practical perspective, but it also provides an insight into likely ADME problems as the hits are evolved into drug-like molecules.
'Furthermore, pharmacophoric enrichment and quality assurance of at least 95 per cent, with full Rule of Three (Ro3) compliance, meant that all fragments used for the study possessed physicochemical properties that also increased the probability of successful hits.' Thermo Fisher Scientific and Dr Myszka are continuing their collaboration as the study now expands to drug development using additional Maybridge Ro3 Fragments.
