'Sieving for gold' in drug candidate selection

Tweeking Nobel prize-winning approaches in order to improve on drug selection protocols. PREMIUM CONTENT

Back in the early ‘90’s, when I was working with Darrell Doyle at SUNY Buffalo, I was searching for the putative membrane iodothyronine/drug transporter in liver and brain tissues. I had already characterized its pharmacophore and was using that knowledge to create affinity columns to select proteins and purify them out of solubulized membranes. I next went to our newly created Monoclonal Research Center to create a library of antibodies that I screened for potency to inhibit thyroid hormone membrane transport in cell culture assays. My team then used these antibodies to identify proteins in our immunoblots.

[Sidebar: Craig Venter was also at SUNY Buffalo then, and using the same monoclonal center for his research. His early research work was on adrenergic receptors.]

It was slow slog to screen all those monoclonals. So I was ectastic when I learned of the breakthrough protocol [at the Society for Neuroscience workshop] using phage display to accelerate the process of sorting and selecting. And I was not at all surprised when it was chosen as part of George Smith’s 2018 Nobel Prize for Chemistry, along with Gregory Winter and Frances Arnold.