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Biochemical assays are commonly used to assess how organic compounds impact the activity of a protein of interest (POI). ZoBio frequently employs biochemical assays to validate compounds that have been identified as interacting with the POI through orthogonal biophysical assays like Surface Plasmon Resonance (SPR) and Nuclear Magnetic Resonance (NMR). To enhance the efficiency and reliability of the biochemical assay workflow, ZoBio has purchased a Dragonfly™ Discovery, a valuable tool known for its ability to significantly improve assay performance by facilitating high-throughput…
Smoothening the Bumpy Road of Covalent Drug Discovery with Protein NMR
Recent years have seen a surge of interest in the use of covalent compounds in small molecule drug discovery. Much of this interest has been driven by the success of covalent compounds for “undruggable” targets such as kRAS. While it is relatively easy to buy or build a library of cysteine reactive compounds and screen them using mass spectrometry (MS), does this really provide all the information to decide whether a “hit” is a good starting point for a drug discovery campaign?
Typically, a covalent campaign starts with screening a library for conjugation…
Compound QC at ZoBio by NMR: Structure Confirmation and Solubility Assay
Just as good quality data is essential to draw the right conclusions from experiments, so are good quality compounds. There are many ways to assess compound quality and one technique we regularly use for this purpose at ZoBio is NMR.
We start by dissolving incoming compounds in d6-DMSO to generate stock solutions for use in various assays. The advantage of using d6-DMSO is that the same stock can not only be used for biochemical and SPR assays, but also for ligand- or protein observed NMR. This way, we reduce batch to batch variance…
Small Molecule Induced Protein Complexes: Gluing the Pieces Together
We typically think of biologically relevant protein complexes forming spontaneously through surface complementarity. However, with the discovery of the mechanism of action (MoA) of Rapamycin & Cyclosporin in the early nineties, it became apparent that protein-protein interactions (PPIs) could be mediated by non-proteinaceous molecules. Furthermore, such interactions could have beneficial pharmacological effects such as the inhibition of the central regulatory kinase mTOR. Since this initial ground-breaking discovery, many other molecules…