東華大學圖書館 |

Language: English

Help

回圖書館首頁

手機版館藏查詢

Back

Switch To: Labeled | MARC Mode | ISBD

Inhibition of late stage enzymes inv...

Helm, Jeremiah Sutter.

Linked to FindBook

Google Book

Amazon

博客來

Inhibition of late stage enzymes involved in peptidoglycan biosynthesis.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Inhibition of late stage enzymes involved in peptidoglycan biosynthesis./
Author:	Helm, Jeremiah Sutter.
Description:	196 p.
Notes:	Source: Dissertation Abstracts International, Volume: 65-06, Section: B, page: 2945.
Contained By:	Dissertation Abstracts International65-06B.
Subject:	Chemistry, Biochemistry. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3135739
ISBN:	0496829548

Inhibition of late stage enzymes involved in peptidoglycan biosynthesis.
Helm, Jeremiah Sutter.

Inhibition of late stage enzymes involved in peptidoglycan biosynthesis. - 196 p.

Source: Dissertation Abstracts International, Volume: 65-06, Section: B, page: 2945.

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

Antibiotic resistance is a growing public health concern. Overuse of antibiotics has led to bacterial strains that are no longer sensitive to the most commonly used drugs. As a result there is a real and pressing need for new antibiotics. By studying the structure and mechanism of the enzymes that are involved in peptidoglycan biosynthesis---an excellent antibiotic target---we can design molecules and assays that might help identify new inhibitors. By studying the structure and mechanism of natural product inhibitors that target the enzymes involved in peptidoglycan biosynthesis, we can design analogues with better antibiotic activity and pharmacological properties. These two approaches are complimentary, and can be used to find inhibitors for the same target.

ISBN: 0496829548Subjects--Topical Terms:

1017722
Chemistry, Biochemistry.

Inhibition of late stage enzymes involved in peptidoglycan biosynthesis.
LDR:03310nmm 2200301 4500 001 1844551
005 20051017073521.5
008 130614s2004 eng d
020 $a 0496829548
035 $a (UnM)AAI3135739
035 $a AAI3135739
040 $a UnM $c UnM
100 1 $a Helm, Jeremiah Sutter. $3 1932742
245 1 0 $a Inhibition of late stage enzymes involved in peptidoglycan biosynthesis.
300 $a 196 p.
500 $a Source: Dissertation Abstracts International, Volume: 65-06, Section: B, page: 2945.
500 $a Adviser: Suzanne Walker.
502 $a Thesis (Ph.D.)--Princeton University, 2004.
520 $a Antibiotic resistance is a growing public health concern. Overuse of antibiotics has led to bacterial strains that are no longer sensitive to the most commonly used drugs. As a result there is a real and pressing need for new antibiotics. By studying the structure and mechanism of the enzymes that are involved in peptidoglycan biosynthesis---an excellent antibiotic target---we can design molecules and assays that might help identify new inhibitors. By studying the structure and mechanism of natural product inhibitors that target the enzymes involved in peptidoglycan biosynthesis, we can design analogues with better antibiotic activity and pharmacological properties. These two approaches are complimentary, and can be used to find inhibitors for the same target.
520 $a MurG is the final intracellular enzyme involved in peptidoglycan biosynthesis. It was long thought that ramoplanin, a lipoglycodepsipeptide antibiotic, inhibited this enzyme. In fact, ramoplanin is often cited as the only known MurG inhibitor. In this thesis, we demonstrate that MurG is not the target for ramoplanin, and that it instead inhibits the extracellular transglycosylase step of peptidoglycan biosynthesis. Synthetic analogues of ramoplanin helped to deconvolute the mechanism of action of this antibiotic, and provide a starting point for further structure-activity relationship studies.
520 $a In addition to being a potential antibiotic target, MurG is a prototypical member of a class of enzymes known as the glycosyltransferases. This family of proteins includes enzymes that play roles in a number of different cellular functions including peptidoglycan biosynthesis, antibiotic synthesis, and cellular signaling. Inhibitors of these enzymes have been difficult to design, and we thought that a high throughput screening approach might provide an alternate means to the previously explored rational design strategies. Based on the MurG crystal structure, we designed and synthesized a fluorescently labeled substrate that was subsequently used for high throughput screening of compound libraries. Putative inhibitors were rescreened for activity against MurG in a purified enzyme assay, and then divided into different structural classes. Due to the structural homology between glycosyltransferases, it is possible that the scaffolds identified in the MurG screen could be elaborated into inhibitors for other enzymes.
590 $a School code: 0181.
650 4 $a Chemistry, Biochemistry. $3 1017722
650 4 $a Chemistry, Pharmaceutical. $3 550957
690 $a 0487
690 $a 0491
710 2 0 $a Princeton University. $3 645579
773 0 $t Dissertation Abstracts International $g 65-06B.
790 1 0 $a Walker, Suzanne, $e advisor
790 $a 0181
791 $a Ph.D.
792 $a 2004
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3135739