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Diversity-oriented synthesis targete...

Tan, Derek Shieh.

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Diversity-oriented synthesis targeted to chemical genetics.

Record Type:	Language materials, printed : Monograph/item
Title/Author:	Diversity-oriented synthesis targeted to chemical genetics./
Author:	Tan, Derek Shieh.
Description:	233 p.
Notes:	Adviser: Stuart L. Schreiber.
Contained By:	Dissertation Abstracts International61-05B.
Subject:	Biology, Genetics. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=9972440
ISBN:	0599777494

Diversity-oriented synthesis targeted to chemical genetics.
Tan, Derek Shieh.

Diversity-oriented synthesis targeted to chemical genetics. - 233 p.

Adviser: Stuart L. Schreiber.

Thesis (Ph.D.)--Harvard University, 2000.

The chemical genetic approach to studying biological systems involves the identification and use of small molecules that can activate or inactivate protein function. The forward chemical genetic approach involves the search for small molecules, beginning with a large random collection, that modulate a specific biological pathway or process. The active small molecule and its protein partner are identified, leading to an understanding of the protein's role in the pathway. In the reverse chemical genetic approach, a small molecule having a known and specific protein target is used to alter the target's function. By determining the pathways and processes affected by the small molecule, the functions of its target can be inferred.

ISBN: 0599777494Subjects--Topical Terms:

1017730
Biology, Genetics.

Diversity-oriented synthesis targeted to chemical genetics.
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020 $a 0599777494
035 $a (UnM)AAI9972440
035 $a AAI9972440
040 $a UnM $c UnM
100 1 $a Tan, Derek Shieh. $3 1257199
245 1 0 $a Diversity-oriented synthesis targeted to chemical genetics.
300 $a 233 p.
500 $a Adviser: Stuart L. Schreiber.
500 $a Source: Dissertation Abstracts International, Volume: 61-05, Section: B, page: 2545.
502 $a Thesis (Ph.D.)--Harvard University, 2000.
520 $a The chemical genetic approach to studying biological systems involves the identification and use of small molecules that can activate or inactivate protein function. The forward chemical genetic approach involves the search for small molecules, beginning with a large random collection, that modulate a specific biological pathway or process. The active small molecule and its protein partner are identified, leading to an understanding of the protein's role in the pathway. In the reverse chemical genetic approach, a small molecule having a known and specific protein target is used to alter the target's function. By determining the pathways and processes affected by the small molecule, the functions of its target can be inferred.
520 $a Chemical genetic approaches allow protein function to be altered rapidly and conditionally. However, they are dependent upon identification of small molecules that bind to proteins with high specificity. Natural products provide many of the most striking examples. Nonetheless, it seems unlikely that natural products alone will provide the hypothetical “complete” set of small molecules that would allow the functions of all proteins to be determined. Efficient methods for discovering this set of small molecules are thus in great demand. Several chemical genetic screens have been developed to address this need. To extend the pool of small molecules available for these screens beyond natural products, organic syntheses must be devised that allow the products to be used effectively in chemical genetic studies.
520 $a We have developed a set of principles and strategies for efficient diversity-oriented synthesis of small molecule libraries targeted to chemical genetics. A library of polycyclics derived from shikimic acid was designed and synthesized in a format compatible with miniaturized chemical genetic assays. A four-step library validation protocol was developed and executed. Molecules in the library were screened for activation of a TGF-β-responsive reporter gene, inhibition or derepression of DNA synthesis, and binding to the KIX domain of CBP. In efforts toward a library of fused cyclic polyethers, a mercury-catalyzed transetherification cyclization reaction was developed. Finally, potential areas of future research in the field are discussed, including a novel convergent approach to library synthesis.
590 $a School code: 0084.
650 4 $a Biology, Genetics. $3 1017730
650 4 $a Chemistry, Organic. $3 516206
690 $a 0369
690 $a 0490
710 2 0 $a Harvard University. $3 528741
773 0 $t Dissertation Abstracts International $g 61-05B.
790 $a 0084
790 1 0 $a Schreiber, Stuart L., $e advisor
791 $a Ph.D.
792 $a 2000
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=9972440