Conditional glycosylate in eukaryotic cells using a biocompatible chemical inducer of dimerization

Jennifer L. Czlapinski; Michael W. Schelle; Lawrence W. Miller; Scott T. Laughlin; Jennifer J. Kohler; Virginia W. Cornish; Carolyn R. Bertozzi

doi:10.1021/ja8037728

Conditional glycosylate in eukaryotic cells using a biocompatible chemical inducer of dimerization

Jennifer L. Czlapinski, Michael W. Schelle, Lawrence W. Miller, Scott T. Laughlin, Jennifer J. Kohler, Virginia W. Cornish, Carolyn R. Bertozzi

Research output: Contribution to journal › Article › peer-review

49 Scopus citations

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.

Original language	English (US)
Pages (from-to)	13186-13187
Number of pages	2
Journal	Journal of the American Chemical Society
Volume	130
Issue number	40
DOIs	https://doi.org/10.1021/ja8037728
State	Published - Oct 8 2008

ASJC Scopus subject areas

Catalysis
General Chemistry
Biochemistry
Colloid and Surface Chemistry

Access to Document

10.1021/ja8037728

Cite this

@article{adc6a5a3d1bf4a75bb4380477f07afe2,

title = "Conditional glycosylate 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.",

author = "Czlapinski, {Jennifer L.} and Schelle, {Michael W.} and Miller, {Lawrence W.} and Laughlin, {Scott T.} and Kohler, {Jennifer J.} and Cornish, {Virginia W.} and Bertozzi, {Carolyn R.}",

year = "2008",

month = oct,

day = "8",

doi = "10.1021/ja8037728",

language = "English (US)",

volume = "130",

pages = "13186--13187",

journal = "Journal of the American Chemical Society",

issn = "0002-7863",

publisher = "American Chemical Society",

number = "40",

}

TY - JOUR

T1 - Conditional glycosylate in eukaryotic cells using a biocompatible chemical inducer of dimerization

AU - Czlapinski, Jennifer L.

AU - Schelle, Michael W.

AU - Miller, Lawrence W.

AU - Laughlin, Scott T.

AU - Kohler, Jennifer J.

AU - Cornish, Virginia W.

AU - Bertozzi, Carolyn R.

PY - 2008/10/8

Y1 - 2008/10/8

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=53549131018&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=53549131018&partnerID=8YFLogxK

U2 - 10.1021/ja8037728

DO - 10.1021/ja8037728

M3 - Article

C2 - 18788807

AN - SCOPUS:53549131018

SN - 0002-7863

VL - 130

SP - 13186

EP - 13187

JO - Journal of the American Chemical Society

JF - Journal of the American Chemical Society

IS - 40

ER -

Conditional glycosylate in eukaryotic cells using a biocompatible chemical inducer of dimerization

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this