Design and synthesis of a cell-permeable synthetic transcription factor mimic.

Design and synthesis of a cell-permeable synthetic transcription factor mimic. Research Abstract Details 

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Design and synthesis of a cell-permeable synthetic transcription factor mimic. Abstract Text:

Xiangshu Xiao,Peng Yu,Hyun-Suk Lim,Devanjan Sikder,Thomas Kodadek,

Synthetic molecules capable of activating the expression of specific genes are of great interest as tools for biological research and, potentially, as a novel class of pharmaceutical agents. It has been demonstrated previously that such synthetic transcription factor mimics (STFMs) can be constructed by connecting a sequence-specific DNA-binding module to a molecule capable of binding to the transcriptional machinery via a suitable linker. These chimeras mimic the two basic properties of native transcription factors, which are able to recognize a promoter sequence specifically and to recruit the transcriptional machinery to that promoter. However, none of the compounds of this type reported to date have been shown to function in living cells. We report here the first example of a cell-permeable STFM that activates the transcription of a reporter gene in mammalian cells. The compound is composed of a cell-permeable coactivator-binding peptoid fused to a DNA-binding hairpin polyamide. The peptoid was identified by screening a combinatorial library of approximately 50,000 compounds for binding to the KIX domain of the CREB-binding protein (CBP), a mammalian transcription coactivator. When incubated with cultured HeLa cells carrying a luciferase reporter plasmid bearing several hairpin polyamide-binding sites, a 5-fold increase in luciferase expression was observed. These experiments set the stage for the identification of hairpin polyamide-peptoid conjugates that are targeted to native genes.

Design and synthesis of a cell-permeable synthetic transcription factor mimic. Publishing Authors By Initials

X Xiao,P Yu,HS Lim,D Sikder,T Kodadek,

For similar genetic processes: gene expression: transcription, genetic research abstracts see: genetic processes: gene expression: transcription, genetic research

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Design and synthesis of a cell-permeable synthetic transcription factor mimic. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Journal of combinatorial chemistry

VOLUME: 9

Page Numbers: 592-600

Journal Abbreviation:

ISSN: 1520-4766

DAY: 27

MONTH: 05

YEAR: 2007

Design and synthesis of a cell-permeable synthetic transcription factor mimic. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 100886263

Design and synthesis of a cell-permeable synthetic transcription factor mimic. Keywords Mesh Terms:

KEYWORDS: Transcription, Genetic

MESH TERMS: genetics

Chemical & Substance for Abstract: Design and synthesis of a cell-permeable synthetic transcription factor mimic. Information

Substance Name: Transcription Factors

Registry Number: 0

Grant and Affiliation Information for Design and synthesis of a cell-permeable synthetic transcription factor mimic.

AFFILIATION: Division of Translational Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, Texas 75390-9185, USA.

Country: United States

AGENCY: United States NIDDK

GRANT: P01-DK58398

ACRONYM: DK

MEDLINETA: J Comb Chem

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