Synthesis and analysis of stabilizing ligands for FKBP-derived destabilizing domains

Bioorg Med Chem Lett. 2008 Jan 15;18(2):759-61. doi: 10.1016/j.bmcl.2007.11.044. Epub 2007 Nov 17.


We recently identified mutants of the human FKBP12 protein that are unstable and rapidly degraded when expressed in mammalian cells. We call these FKBP mutants destabilizing domains (DDs), because their instability is conferred to any protein fused to the DDs. A cell-permeable ligand binds tightly to the DDs and prevents their degradation, thus providing small molecule control over intracellular protein levels. We now report the synthesis and functional characterization of a stabilizing ligand called Shield-2. The synthesis of Shield-2 is efficient, and this ligand binds to the FKBP(F36V) protein with a dissociation constant of 29 nM.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Humans
  • Ligands
  • Mice
  • Tacrolimus Binding Proteins / chemistry*


  • Ligands
  • Tacrolimus Binding Proteins