Hydrophobic Tagging

Mimicking Protein Denaturation to Induce Protein Degradation

With the goal of controlling intracellular protein levels using small molecules, we have shown that appending a hydrophobic moiety to the surface of a protein can lead to its degradation.  This hydrophobic tagging approach co-opts the intracellular protein quality control mechanisms by mimicking the internal hydrophobic amino acid side chains, which are exposed to cellular chaperones upon protein denaturation.

Relevant Publications:

Neklesa TK, Crews CM
Nature 2012 487 19 308-309
Tae H-S, Sundberg TB, Neklesa TK, Noblin DJ, Gustafson JL, Roth AG, Raina K, Crews CM
ChemBioChem 2012 13 4 538-541
Neklesa TK, Tae HS, Schneekloth AR, Stulberg MJ, Corson TW, Sundberg TB, Raina K, Holley SA, Crews CM
Nat Chem Biol 2011 7 8 538-43