Gas Phase Drug Screening

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Science  05 Nov 2004:
Vol. 306, Issue 5698, pp. 943
DOI: 10.1126/science.306.5698.943d

Membrane proteins are prime drug targets, yet are fabulously difficult to work with because their structures are stabilized by both hydrophobic and hydrophilic interactions (with lipids, charged solutes, and water). These kinds of interactions need to be maintained in order to preserve functional integrity, such as the binding of small-molecule ligands, and this has meant coping with sample heterogeneity in the form of native and exogenous lipids and detergents. Ilag et al. have overcome these obstacles and developed an approach for characterizing the binding of the artificial substrate tetraphenyl phosphonium to the bacterial multidrug transporter EmrE in a dodecylmaltoside-solubilized state. Tandem mass spectrometry led to the identification of a broad peak at 6500 to 6800 m/z that contains protein, detergent, and ligand, with these components being dissociable from the parent complex in reverse order as the collision voltage was increased. — GJC

J. Am. Chem. Soc. 10.1021/ja0450307 (2004).

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