Thursday, July 7, 2011

The peculiar story of PTC124

Several years ago a very, very cool drug was discovered - PTC124. This one was inhibiting NMD (nonsense mediated mRNA decay), and since NMD is implicated in several deseases, PTC124 was of great interest. I have discussed this story here.

Well, it seems that there is a twist in this story. PTC124 was discovered using firefly luciferase (FLuc) as a reporter. And now is seems that it rather than acting on the NMD level, PTC124 interacts with the FLuc itself and modulates its activity!

What's especially interesting, is that work on PTC124 continues, and many more papers are getting published, not necessarily using FLuc... So what was it? Just a fluke?

...this story is somehow similar to that one.

References:

Auld, D. S., Lovell, S., Thorne, N., Lea, W. A., Maloney, D. J., Shen, M., Rai, G., et al. (2010). Molecular basis for the high-affinity binding and stabilization of firefly luciferase by PTC124 Proceedings of the National Academy of Sciences of the United States of America, 107(11), 4878–4883. PIMD 20194791

Auld, D. S., Thorne, N., Maguire, W. F., & Inglese, J. (2009). Mechanism of PTC124 activity in cell-based luciferase assays of nonsense codon suppression Proceedings of the National Academy of Sciences of the United States of America, 106(9), 3585–3590. PIMD 19208811

2 comments:

  1. I have been wondering the same thing...what's going on?

    ReplyDelete
  2. A mystery of sorts, that's what's going on.

    ReplyDelete