2. Academic Validation
  3. Engineering small molecule specificity in nearly identical cellular environments

Engineering small molecule specificity in nearly identical cellular environments

  • Bioorg Med Chem Lett. 2007 May 15;17(10):2703-5. doi: 10.1016/j.bmcl.2007.03.012.
Mark A Sellmyer 1,  Kryn Stankunas,  Roger Briesewitz,  Gerald R Crabtree,  Thomas J Wandless
Affiliations

Affiliation

  • 1 Department of Chemical and Systems Biology, Stanford University, Stanford, CA 94305, USA.
PMID: 17383876 DOI: 10.1016/j.bmcl.2007.03.012
Abstract

Methotrexate (MTX), an inhibitor of dihydrofolate reductase, was tethered to an FKBP12 ligand (SLF), and the resulting bifunctional molecule (MTXSLF) potently inhibits either Enzyme but not both simultaneously. MTXSLF is cytotoxic to fibroblasts derived from FKBP12-null mice but is detoxified 40-fold by FKBP12 in wild-type fibroblasts. These studies demonstrate that non-target proteins in an otherwise identical genetic background can be used to predictably regulate the biological activity of synthetic molecules.

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