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Conditional glycosylation in eukaryotic cells using a biocompatible chemical inducer of dimerization.

ABSTRACT: Chemical inducers of dimerization (CIDs) are cell-permeable small molecules capable of dimerizing two protein targets. The most widely used CID, the natural product rapamycin and its relatives, is immunosuppressive due to interactions with endogenous targets and thus has limited utility in vivo. Here we report a new biocompatible CID, Tmp-SLF, which dimerizes E. coli DHFR and FKBP and has no endogenous mammalian targets that would lead to unwanted in vivo side effects. We employed Tmp-SLF to modulate gene expression in a yeast three-hybrid assay. Finally, we engineered the Golgi-resident glycosyltransferase FucT7 for tunable control by Tmp-SLF in mammalian cells.

SUBMITTER: Czlapinski JL

PROVIDER: S-EPMC2709988 | biostudies-literature | 2008 Oct

REPOSITORIES: biostudies-literature

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Conditional glycosylation in eukaryotic cells using a biocompatible chemical inducer of dimerization.

Czlapinski Jennifer L JL Schelle Michael W MW Miller Lawrence W LW Laughlin Scott T ST Kohler Jennifer J JJ Cornish Virginia W VW Bertozzi Carolyn R CR

Journal of the American Chemical Society 20080913 40

Chemical inducers of dimerization (CIDs) are cell-permeable small molecules capable of dimerizing two protein targets. The most widely used CID, the natural product rapamycin and its relatives, is immunosuppressive due to interactions with endogenous targets and thus has limited utility in vivo. Here we report a new biocompatible CID, Tmp-SLF, which dimerizes E. coli DHFR and FKBP and has no endogenous mammalian targets that would lead to unwanted in vivo side effects. We employed Tmp-SLF to mod ...[more]

PMID: 18788807

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