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Biased small molecule libraries :Encoding strategies, pathway development, and diversity-oriented synthesis

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Biased small molecule libraries :
其他題名:	Encoding strategies, pathway development, and diversity-oriented synthesis
作者:	Perez Fernandez, Lucy.
面頁冊數:	221 p.
附註:	Adviser: Stuart L. Schreiber.
附註:	Source: Dissertation Abstracts International, Volume: 65-05, Section: B, page: 2423.
Contained By:	Dissertation Abstracts International65-05B.
標題:	Chemistry, Organic.
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3131952
ISBN:	0496791923

Biased small molecule libraries :Encoding strategies, pathway development, and diversity-oriented synthesis
Perez Fernandez, Lucy.

Biased small molecule libraries :Encoding strategies, pathway development, and diversity-oriented synthesis [electronic resource] - 221 p.

Adviser: Stuart L. Schreiber.

Thesis (Ph.D.)--Harvard University, 2004.

An efficient and accessible approach to split-pool, diversity-oriented synthesis using high-capacity polystyrene (PS) macrobeads as individual microreactors has been developed for converting high-capacity beads into arrays of stock solutions of predominantly single compounds suitable for many phenotypic and protein-binding assays. This "one-bead, one-stock solution" strategy is a central element of a technology platform aimed at advancing chemical genetics. Herein are full details of the development of a reliable library encoding strategy and the design of compound decoding methods, both from PS macrobeads and stock solutions of small molecules cleaved from PS macrobeads.

ISBN: 0496791923Subjects--Topical Terms:

193634
Chemistry, Organic.

Biased small molecule libraries :Encoding strategies, pathway development, and diversity-oriented synthesis
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520 # $a An efficient and accessible approach to split-pool, diversity-oriented synthesis using high-capacity polystyrene (PS) macrobeads as individual microreactors has been developed for converting high-capacity beads into arrays of stock solutions of predominantly single compounds suitable for many phenotypic and protein-binding assays. This "one-bead, one-stock solution" strategy is a central element of a technology platform aimed at advancing chemical genetics. Herein are full details of the development of a reliable library encoding strategy and the design of compound decoding methods, both from PS macrobeads and stock solutions of small molecules cleaved from PS macrobeads.
520 # $a In chemical genetics, small molecules, instead of genetic mutations, are used to modulate the functions of proteins rapidly and conditionally, thereby allowing many biological processes to be explored. This approach requires the identification of small molecules that modulate pathways and bind to proteins with high specificity. Structurally complex and diverse small molecules can be prepared using diversity-oriented synthesis, and the split-pool strategy allows many such compounds to be spatially segregated on individual polymer beads.
520 # $a This thesis also describes the solid-phase syntheses of three related libraries of small molecules to identify selective histone deacetylase (HDAC) inhibitors based on the structure of trichostatin A, a known nonspecific inhibitor of HDACs. Methods were developed for solid-phase asymmetric allylborations with enantiomerically pure diisopinocampheylborane-derived reagents to introduce the element of stereochemical diversity in these synthetic pathways. The syntheses differ in terms of the polymeric support chosen, the reaction pathway, and the types of assays that the library products can be used for. These differences serve to highlight the challenges faced by chemists in planning and executing diversity-oriented syntheses and how these can be addressed.
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