2. Academic Validation
  3. Regulation of gene expression by synthetic dimerizers with novel specificity

Regulation of gene expression by synthetic dimerizers with novel specificity

  • Bioorg Med Chem Lett. 2003 Oct 6;13(19):3181-4. doi: 10.1016/s0960-894x(03)00707-8.
Wu Yang 1,  Terence P Keenan,  Leonard W Rozamus,  Xiurong Wang,  Victor M Rivera,  Carl T Rollins,  Tim Clackson,  Dennis A Holt
Affiliations

Affiliation

  • 1 ARIAD Gene Therapeutics, Inc., 26 Landsdowne Street, Cambridge, MA 02139-4234, USA.
PMID: 12951089 DOI: 10.1016/s0960-894x(03)00707-8
Abstract

New synthetic chemical inducers of dimerization, comprising homodimeric FKBP ligands with engineered specificity for the designed point mutant F36V, have been evaluated for inducing targeted gene expression in mammalian cells. Structure-activity studies indicated that high-affinity dimerizers such as AP1903 are ineffective, perhaps due to kinetic trapping of non-productive dimers, whereas lower-affinity molecules, exemplified by AP1889 and AP1966, potently activate transcription.

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