東華大學圖書館 |

語系: 繁體中文

說明(常見問題)

回圖書館首頁

手機版館藏查詢

登入

回首頁

切換: 標籤 | MARC模式 | ISBD

Discovery of O-GlcNAc transferase in...

Gross, Benjamin Jared.

FindBook

Google Book

Amazon

博客來

Discovery of O-GlcNAc transferase inhibitors.

紀錄類型:	書目-語言資料,印刷品 : Monograph/item
正題名/作者:	Discovery of O-GlcNAc transferase inhibitors./
作者:	Gross, Benjamin Jared.
面頁冊數:	142 p.
附註:	Adviser: Suzanne Walker.
Contained By:	Dissertation Abstracts International68-05B.
標題:	Chemistry, Biochemistry. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3264970
ISBN:	9780549036128

Discovery of O-GlcNAc transferase inhibitors.
Gross, Benjamin Jared.

Discovery of O-GlcNAc transferase inhibitors. - 142 p.

Adviser: Suzanne Walker.

Thesis (Ph.D.)--Harvard University, 2007.

O-GlcNAc transferase (OGT) is an essential eukaryotic glycosyltransferase that catalyzes the addition of a single O-linked-GlcNAc to serine and threonine residues of many nuclear and cytosolic proteins. This dynamic, intracellular glycosylation (O-GlcNAcylation) is involved in numerous and diverse cell signaling pathways and appears to act as a nutrient sensor and an indicator of cell stress. Increased OGT activity resulting from hyperglycemia has been implicated in the development of diabetic complications and in peripheral insulin resistance, which is a hallmark of Type 2 diabetes. It is hypothesized that reducing OGT activity could ameliorate insulin resistance and complications that result from the diabetic state. This work is aimed at developing selective OGT inhibitors to test this hypothesis.

ISBN: 9780549036128Subjects--Topical Terms:

1017722
Chemistry, Biochemistry.

Discovery of O-GlcNAc transferase inhibitors.
LDR:03358nam 2200325 a 45 001 962699
005 20110830
008 110831s2007 ||||||||||||||||| ||eng d
020 $a 9780549036128
035 $a (UMI)AAI3264970
035 $a AAI3264970
040 $a UMI $c UMI
100 1 $a Gross, Benjamin Jared. $3 1285759
245 1 0 $a Discovery of O-GlcNAc transferase inhibitors.
300 $a 142 p.
500 $a Adviser: Suzanne Walker.
500 $a Source: Dissertation Abstracts International, Volume: 68-05, Section: B, page: 3027.
502 $a Thesis (Ph.D.)--Harvard University, 2007.
520 $a O-GlcNAc transferase (OGT) is an essential eukaryotic glycosyltransferase that catalyzes the addition of a single O-linked-GlcNAc to serine and threonine residues of many nuclear and cytosolic proteins. This dynamic, intracellular glycosylation (O-GlcNAcylation) is involved in numerous and diverse cell signaling pathways and appears to act as a nutrient sensor and an indicator of cell stress. Increased OGT activity resulting from hyperglycemia has been implicated in the development of diabetic complications and in peripheral insulin resistance, which is a hallmark of Type 2 diabetes. It is hypothesized that reducing OGT activity could ameliorate insulin resistance and complications that result from the diabetic state. This work is aimed at developing selective OGT inhibitors to test this hypothesis.
520 $a In Chapter Two, the gene synthesis and heterologous expression of human OGT in E. coli is described. This work is the only reported system capable of expressing large quantities of this enzyme, which is required for both high-throughput screening and structural studies of OGT.
520 $a In Chapter Three, a donor substrate-analog displacement assay was developed for OGT and a high throughput screen was implemented against &sim;64,000 small molecules. Hits from this screen were shown to inhibit OGT turnover in vitro, and several of these inhibitors attenuate O-GlcNAcylation in cell culture. Many of the inhibitors clustered into two structural classes.
520 $a In Chapter Four, the development of a homogenous, kinetic OGT assay and subsequent high throughput screening efforts are described. Assaying over 130,000 small molecules revealed inhibitors with high potency, including one compound with an IC50 &sim; 900 nM. These hits also clustered into several structural scaffolds, distinct from those found in Chapter Three.
520 $a The discovery of OGT inhibitors and inhibitor scaffolds from these assays provide starting points to probe the biology and pathology of O-GlcNAcylation using small molecules. Moreover, the high throughout screening approaches described in this work are widely applicable to many additional glycosyltransferases, a class of enzymes that number over 12,000 and are involved in diverse biological processes. Remarkably few inhibitor scaffolds exist for this enzyme class, and there are virtually no reported strategies to find new ones. This work enables the discovery of novel inhibitor scaffolds for this large class of enzymes.
590 $a School code: 0084.
650 4 $a Chemistry, Biochemistry. $3 1017722
650 4 $a Chemistry, Pharmaceutical. $3 550957
690 $a 0487
690 $a 0491
710 2 $a Harvard University. $3 528741
773 0 $t Dissertation Abstracts International $g 68-05B.
790 $a 0084
790 1 0 $a Walker, Suzanne, $e advisor
791 $a Ph.D.
792 $a 2007
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3264970