Recent Experiments

Short form TGFBR1 (ALK5) purification and co-crystallisation with M4K2006 and M4K2089

In the absence of our “workhorse” protein, ACVR1 residues 208-499 (constitutively active Q207D mutant) (as we are still trying to work out why it won’t express at the moment), and the complete lack of crystals/diffracting crystals for the TGFBR1/FKBP12 complex, I have shifted to some other constructs we have to keep things moving. I had Read More …

CaMKK2 Inhibitors: Building Diversity Around the Core Furopyridine Scaffold

Preparation of CaMKK2 analogs Pursuant to our aim of preparing a library of small molecule chemical probes around our most promising core scaffold, furopyridine, we sought to develop different chemistries that would allow us to achieve this objective. In the original synthetic route, 5-bromofuro[2,3-b]pyridine, 1, was able to undergo the Suzuki cross-coupling reaction to install Read More …

Purification and crystallisation of ALK2 (R206H mutation) with M4K Pharma compounds.

As part of an ongoing collaboration with Meds4Kids Pharma (M4KPharma), we are testing a range of compounds identified and generated by them as being of interest in developing a molecule specific against ALK2 that has the right properties help treat some cases of DIPG. This also has significant implications for development of a drug that Read More …

Purification of Recombinant Cas9

These days CRISPR gene editing needs little introduction. From humble origins as a bacterial defence system evolved to thwart viral invaders, CRISPR-based technologies have recently made headlines for their promise to revolutionize medicine. While there is a lot of excitement surrounding the use of gene editing in the clinic, it is also an incredibly valuable tool for studying the Read More …

Still no protein, and no diffraction from TGFBR1/FKBP12 crystals, but outreach is fun!

I’m sad to report that a couple of test expressions later, we’re still no wiser as to why ACVR1 isn’t expressing. It’s worked on a couple of small scale expression test plates, but just doesn’t want to scale up anymore. We may be looking at having to remake the virus. In the meantime, I had Read More …