Skip to main content

Protein – You may know it as a morning protein shake or your essential gym friend, but did you also know that a lot of diseases are linked to proteins? Diseases such as Alzheimer’s, cancer, and ALS (which you may remember from the ice-bucket challenge) are all linked to group of proteins known as intrinsically disordered proteins (or IDPs for short). IDPs normally play role in carrying signal, so in these diseases something goes wrong, and they no longer perform their job well.

How can we find drugs to stop IDPs that goes wrong is the logical question? The answer: that’s tricky as IDPs have a lot of shapes, which is helpful for their job in carrying signal but makes drugging them very very challenging. In this paper, we chose an IDP called the androgen receptor which is involved in prostate cancer, and we wanted to test our method and its capabilities to shed light on this IDP interaction with drugs. Our main questions were: can we see the interaction? Does said interaction capture the IDP in one of its shapes? Can we see the preferred shape?

To answer our questions, we employed our method native ion mobility mass spectrometry (IM-MS), which is a method that looks at protein sizes and shapes. We examined the interaction between androgen receptor and the drug (EPI-001), and we were able to answer our questions:

  • Can we see the interaction? Yes, we can (Figure 2 & Figure 3).
  • Does said interaction capture the IDP in one of its shapes? Yes, it does (Figure 4 & Figure 5).
  • Can we see the preferred shape?  Yes (Figure 4 & Figure 5).    

So, if you have an IDP (which as we established is associated with a disease) and you would like to test its drugability in a quick manner without consuming large quantities of your precious sample, what’s stopping you from using IM-MS?

This work was led by Ikhlas Ahmed who is a post-doc under the supervision of Rebecca Beveridge.
You can read the paper here.