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The Trouble with Membranes

Membrane proteins comprise the majority of drug targets.

Written byAileen Constans
| 3 min read

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Courtesy of Steve Zweig

Membrane proteins comprise the majority of drug targets. So naturally, the protein biochip industry is keen to array them. But membrane protein arrays have been difficult to build, because these proteins are notoriously tough to stabilize. Now a group of investigators is working to overcome this problem.

Steve Zweig of Molecular Pathways, which recently patented a technique for studying drug candidate binding to G protein-coupled receptors (GPCRs) in an array format,1 says previous attempts to make membrane protein microarrays failed because of steric problems. With the membranes positioned only nanometers from the array substrate surface, the receptors' cytoplasmic domains (which protrude below the lipid bilayer) were distorted and rendered inert.

Membrane proteins are laterally mobile within the membrane, says Zweig, so any microarray technology has to allow for such movement. "Because the membrane receptors were sort of moving parallel to the support, there really wasn't any ...

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