Wednesday, May 14, 2014

How Are Researchers Using Bioorthogonal Reactions as Experimental Tools?

Carolyn Bertozzi is a leading expert on bioorthogonal chemistry.  In fact, she is credited with developing the field.  She’ll be keynoting on Bioorthogonal Chemistries for Biomolecular Engineering at this year’s Bioconjugates: From Targets to Therapeutics conference.  We were able to pick Carolyn’s brain about some of the issues in the field today.  One of our questions to her:

How exactly are researchers using these bioorthogonal reactions as experimental tools?
Well, it has turned out to be a pretty general platform for use in bioconjugation in many different kinds of settings. For example, from the perspective of making chemically modified protein drugs, which is a major component of biopharma efforts, bioorthogonal chemistry is really useful.

So, people have used it to attach bio-ethylene glycol change to proteins. So, it’s a PEGylate protein. In many ways, using bioorthogonal chemistry to generate such chemically modified proteins is much cleaner and easier to control than more conventional chemistries of bioconjugation, like the kinds of chemistries that involve the side chains of glycines and cysteines; these are much harder to control. Just to modify a protein with a cargo molecule, whether it’s for a therapeutic purpose like an antibody drug conjugate, which is going to be the subject of my presentation, or for PEGylation or even just to attach biophysical probes to proteins, like a fluorescent die for imaging purposes or cystoscopy purposes. These are all areas in which bioorthogonal chemistries turned out to be quite useful.

Beyond that, it’s turned out to be a really nice experimental platform for in vivo imaging in live cells and also live organisms. There has been a lot of activity in basically delivering a bioorthogonal functional group to a protein or a nucleic acid or a polysaccharide in the context of live cells or model organisms and then using the bioorthogonal chemistry to conjugate that functional group with a probe molecule in the living system. Because the chemistry is orthogonal to the biology, you can actually do these reactions in organisms without any unwanted side effects or off-target reactivity. So, in my lab we use bioorthogonal chemistry to image self-surface sugar molecules.  That’s an interest of ours. 

We, in other labs, have used bioorthogonal chemistry to image bacterial pethano glycan and to look at the dynamic nature of that structure in the context of pathogenesis. People have used bioorthogonal chemistry to image proteins that had been recently biosynthesized to understand how protein biosynthesis changes as a function of time during physiological process or as a function of space across different components of the cell.  

So, I think imaging and bioconjugation or making chemically modified protein drugs, these are the big applications that I’ve been reading about in recent years.

Click here to download the entire podcast and hear more from Carolyn.

You can hear more from Carolyn at this year’s Bioconjugates: From Targets to Therapeutics conference, June 4-6th, San Francisco, CA.  SAVE 20% on the standard rate. Use discount code D14199BLOG. Register here

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