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…
Contributing All the Way to the Clinic
Recently the ZoBio team made an important contribution to a drug discovery project for our client Mirati Therapeutics that we are particularly proud of and has had significant impact [1]. This work describes a program to develop inhibitors of the epigenetic target PRMT5 with the potential to …
The Insidious Underbelly of Protein Aggregation
It is well known, and accepted, that it is essential to have “high quality” protein at the outset of a target based, small molecule drug discovery campaign. But what does “high quality” mean?
Certainly biological activity is a must. A high degree of purity (typically ≥95%) is another crucial requirement. Most often “purity” is defined based on the presence of other proteins in the preparation, but the presence of small molecules, whether or not of biological origin, also needs to be considered. However, the aggregation state is only rarely considered, and yet it significantly impacts…