Synthesis of Diverse Lactam Carboxamides Leading to the Discovery of a New Transcription-Factor Inhibitor

Diversity is the key: Skeletal diversity is a useful starting point in the search for compounds that modulate protein–biopolymer interactions. A library of 400 lactam carboxamides has been synthesized in a short synthetic sequence and a new compound that inhibits the interaction of a transcription f...

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Bibliographic Details
Published inAngewandte Chemie (International ed.) Vol. 46; no. 28; pp. 5352 - 5355
Main Authors Ng, Pui Yee, Tang, Yuchen, Knosp, Wendy M, Stadler, H. Scott, Shaw, Jared T
Format Journal Article
LanguageEnglish
Published Weinheim Wiley-VCH Verlag 2007
WILEY-VCH Verlag
WILEY‐VCH Verlag
Subjects
Amides - chemical synthesis
Amides - chemistry
Carboxylic Acids - chemistry
combinatorial chemistry
DNA
DNA - chemistry
DNA - metabolism
gene expression
Homeodomain Proteins - chemistry
Homeodomain Proteins - metabolism
lactams
Lactams - chemistry
Models, Molecular
Molecular Structure
proteins
Stereoisomerism
Transcription Factors - antagonists & inhibitors
Transcription Factors - metabolism
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Summary:Diversity is the key: Skeletal diversity is a useful starting point in the search for compounds that modulate protein–biopolymer interactions. A library of 400 lactam carboxamides has been synthesized in a short synthetic sequence and a new compound that inhibits the interaction of a transcription factor (HOXA13) with its DNA target has been discovered, and inhibition of transcription is demonstrated in cells.
Bibliography:http://dx.doi.org/10.1002/anie.200700762
Shriners Hospital for Children
This work was conducted under the aegis of the Broad Institute Center for Methodology and Library Development (CMLD, NIGMS P50 GM069721). The HOXA13 small molecule screen was supported by a grant from the Shriners Hospital for Children (H.S.S.). The project has been funded in part with Federal funds from the NCI's Initiative for Chemical Genetics, NIH under Contract No. N01-CO-12400. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Service, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. The authors thank Prof. Stuart Schreiber (Harvard University, Broad Institute, and Howard Hughes Medical Institute) for insightful discussions.
Broad Institute Center for Methodology and Library Development (CMLD - No. NIGMS P50 GM069721
ArticleID:ANIE200700762
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NIH - No. N01-CO-12400
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NCI's Initiative for Chemical Genetics
This work was conducted under the aegis of the Broad Institute Center for Methodology and Library Development (CMLD, NIGMS P50 GM069721). The HOXA13 small molecule screen was supported by a grant from the Shriners Hospital for Children (H.S.S.). The project has been funded in part with Federal funds from the NCI's Initiative for Chemical Genetics, NIH under Contract No. N01‐CO‐12400. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Service, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. The authors thank Prof. Stuart Schreiber (Harvard University, Broad Institute, and Howard Hughes Medical Institute) for insightful discussions.
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SourceType-Scholarly Journals-1
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ISSN:1433-7851
1521-3773
DOI:10.1002/anie.200700762