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J. Biol. Chem., Vol. 277, Issue 40, 37512-37518, October 4, 2002
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From Rigel, Inc., South San Francisco, California 94080
Inteins are polypeptide sequences found in a
small set of primarily bacterial proteins that promote the splicing of
flanking pre-protein sequences to generate mature protein products.
Inteins can be engineered in a "split and inverted" configuration
such that the protein splicing product is a cyclic polypeptide
consisting of the sequence linking two intein subdomains. We have
engineered a split intein into a retroviral expression system to enable
the intracellular delivery of a library of random cyclic peptides in
human cells. Cyclization of peptides could be detected in cell lysates
using mass spectrometry. A functional genetic screen to identify
5-amino acid-long cyclic peptides that block interleukin-4 mediated IgE class switching in B cells yielded 13 peptides that selectively inhibited germ line
Retrovirally Delivered Random Cyclic Peptide Libraries Yield
Inhibitors of Interleukin-4 Signaling in Human B Cells*
,
,
transcription. These results demonstrate the generation of cyclic peptide libraries in human cells
and the power of functional screening to rapidly identify biologically
active peptides.
*
The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
These authors contributed equally to this work.
§
Present address: Dept. of Biology, Massachusetts Inst. of
Technology, Cambridge, MA 02139-4307.
¶
To whom correspondence should be addressed: Rigel, Inc., 240 East Grand Ave., South San Francisco, CA 94080. Tel.: 650-624-1102; Fax: 650-624-1133; E-mail: dgpayan@rigel.com.
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