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:

Gustafson JL, Neklesa TK, Cox CS, Roth AG, Buckley DL, Tae HS, Sundberg TB, Stagg B, Hines J, McDonnell DP, Norris JD, Crews CM.
Angewandte Chemie Int. Ed. Engl. 2015 doi:10.1002/anie.201503720
Lim SM, Xie T, Westover KD, Ficarro SB, Tae HS, Gurbani D, Sim T, Marto JA, Janne PA, Crews CM, Gray NS
Bioorganic and Medicinal Chemistry Letters 2015 doi: http://dx.doi.org/10.1016/j.bmcl.2015.04.103
Raina K, Noblin DJ, Serebrenik YV, Adams A, Zhao C, Crews CM.
Nature Chemical Biology 2014 10 11 957-962
Xie T, Lim SM, Westover K, Dodge ME, Ercan D, Ficarro SB, Udayakumar D, Riddle SM, Marto JA, Janne PA, Crews CM, Gray NS
Nature Chemical Biology 2014 10 1006-1012
Neklesa TK, Noblin DJ, Kuzin A, Lew S, Seetharaman J, Acton TB, Kornhaber G, Xiao R, Montelione GT, Tong L, Crews CM.
ACS Chemical Biology 2013 8 10 2293-2300