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Regulation of gene expression by synthetic dimerizers with novel specificity

✍ Scribed by Wu Yang; Terence P. Keenan; Leonard W. Rozamus; Xiurong Wang; Victor M. Rivera; Carl T. Rollins; Tim Clackson; Dennis A. Holt

Publisher: Elsevier Science
Year: 2003
Tongue: English
Weight: 156 KB
Volume: 13
Category: Article
ISSN: 0960-894X
DOI: 10.1016/s0960-894x(03)00707-8

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✦ Synopsis

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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