December 21, 2009

In its December 21, 2009 issue, Chemical & Engineering News recognized recent discoveries in the laboratory of Steve Metallo, associate professor of chemistry, and collaborators as one of twelve “superlative achievements” in chemistry research for 2009.

In its News of the Week section of its June 1, 2009 issue, Chemical & Engineering News featured work ongoing in the Metallo lab on small molecule binding to intrinsically disordered proteins.

According to the editor’s in Chemical Year in Review 2009, “CE&N produces 51 issues each year containing several hundred articles about important research advances in Chemistry.”

The recognition in C&E News reads:

DISORDERLY PROTEINS TURN PREDICTABLE

Floppy, unstructured proteins, despite their lack of defined nooks and crannies, still contain regions that are prone to binding small molecules, researchers learned this year. The findings provide a potential general approach to predicting binding sites on disordered proteins and finding small-molecule drugs to target them. Intrinsically disordered proteins play fundamental roles in biology, such as in gene transcription and cell division, but researchers don’t have a straightforward way of pinpointing molecules that alter their activity.

Steven J. Metallo of Georgetown University, Edward V. Prochownik of the University of Pittsburgh Medical Center, and coworkers outlined a way to do just that (C&EN, June 1, page 5; J. Am. Chem. Soc. 2009, 131, 7390). The team studied a segment of a disordered transcription factor protein called c-Myc, which is implicated in multiple cancers. Prochownik’s group previously found seven structurally diverse c-Myc inhibitors. In the new study, the team found three hydrophobic peptide stretches on c-Myc that recognize those inhibitors. Their results explain the specificity of the inhibitors and suggest ways of finding more. Since the study came out, Metallo and coworkers have found that they can link two of the inhibitors together and gain three orders of magnitude in affinity for c-Myc, which remains disordered even in the tight complex.