A growing team of groundbreaking scientists around the world are now sharing their lab notebooks online
Hello everyone and happy New Year! I really, really wanted to end the year on a high note in December before I went off on holiday, but as it turned out, I didn’t have enough time to set up 18 plates and write a blog post on the last day. So I’ll just have to Read More …
At SGC we are interested in developing protein kinase inhibitors with a high selectivity towards other protein kinases. Based on lead compounds from the literature and our group new and selective CDKL2 inhibitors should be designed, synthesized and tested. Carla Alamillo, a former member of our group, worked on this topic and mentioned in her Read More …
In an effort to develop clinical compounds for Diffused Intrinsic Pontine Glioma (DIPG) treatment, new analogues of ACVR1/ALK2 inhibitors are continuously synthesised by Ontario Institute for Cancer Research (OICR) and Charles River Laboratories (CRL). I will provide prompt feedback of the cellular assay results to guide their design of new compounds. I determined the potency Read More …
The year is coming to an end and I want to start my blog by giving you an overview of a project that kept me busy for the better part of it. Our existing Protein Data Bank (PDB) batch deposition mechanism underwent a major overhaul recently and we are finally in a position where we Read More …
Hello again! A few posts ago (here), I presented one fragment bound at the interface between two subunits of the HAO1 tetramer (figure 1 will refresh your memory). Our idea to optimize this fragment into an inhibitor would be to make it bigger so that it disrupts the HAO1 tetramer. I would expect this to Read More …
In a previous post, I described the importance of solving the structure of other USPs that have a Zf-UBD for the rational design of selective compounds. The last post described the design, cloning, E.coli expression, growth and purification of some of the USP Zf-UBD constructs. As a continuation in my quest to try and crystallize Read More …
One problem with working with the isolated kinase domains of ALK2 and it’s type II binding partners, is that the affinity between the kinase domains alone is insufficient to allow complex formation. We know that the two proteins associate with each other in vivo and are co-localised by the domains on the outside of the Read More …
Continuing with the line of delivering a chemical probe for DRAK2/STK17B kinase, we decided to revise the procedure to synthesize analogs with a thieno[2,3-d]pyrimidine core, which are intended to be used as negative control in our DRAK2 inhibition study. We shortened the synthesis of these pyrimidines to 2 steps from the starting material 6-bromo-4-chlorothieno[2,3-d]pyrimidine 1 Read More …
Manuscript finished! Design and characterisation of mutant and wild-type huntingtin proteins produced from a toolkit of scalable eukaryotic expression systems
Hi there! The last month of my life was taken over by making sure my PhD first year report was beautifully polished, but I have returned with results of a small compound screen: These are all compounds that Jong Fu has already tested with his assays so we know they effectively inhibit ACVR1, but I Read More …
