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

The effects of partial denaturation ...

Vernaglia, Brian Anthony.

Linked to FindBook

Google Book

Amazon

博客來

The effects of partial denaturation on in vitro fibril formation.

Record Type:	Electronic resources : Monograph/item
Title/Author:	The effects of partial denaturation on in vitro fibril formation./
Author:	Vernaglia, Brian Anthony.
Description:	190 p.
Notes:	Source: Dissertation Abstracts International, Volume: 65-03, Section: B, page: 1439.
Contained By:	Dissertation Abstracts International65-03B.
Subject:	Engineering, Chemical. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3124799
ISBN:	9780496721030

The effects of partial denaturation on in vitro fibril formation.
Vernaglia, Brian Anthony.

The effects of partial denaturation on in vitro fibril formation. - 190 p.

Source: Dissertation Abstracts International, Volume: 65-03, Section: B, page: 1439.

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

Many proteins are prone to misfolding and aggregating into amyloid fibrils. Fibrils are ordered aggregates composed of cross beta-sheets that form long, non-branching fibers approximately 60 to 120 A in diameter. The formation of amyloid fibrils is an intractable problem that can result in decreased pharmaceutical shelf life in vitro and serious illness or death in vivo.

ISBN: 9780496721030Subjects--Topical Terms:

1018531
Engineering, Chemical.

The effects of partial denaturation on in vitro fibril formation.
LDR:03300nmm 2200325 4500 001 1820960
005 20061110073008.5
008 130610s2004 eng d
020 $a 9780496721030
035 $a (UnM)AAI3124799
035 $a AAI3124799
040 $a UnM $c UnM
100 1 $a Vernaglia, Brian Anthony. $3 1910156
245 1 4 $a The effects of partial denaturation on in vitro fibril formation.
300 $a 190 p.
500 $a Source: Dissertation Abstracts International, Volume: 65-03, Section: B, page: 1439.
500 $a Adviser: Eliana De Bernardez Clark.
502 $a Thesis (Ph.D.)--Tufts University, 2004.
520 $a Many proteins are prone to misfolding and aggregating into amyloid fibrils. Fibrils are ordered aggregates composed of cross beta-sheets that form long, non-branching fibers approximately 60 to 120 A in diameter. The formation of amyloid fibrils is an intractable problem that can result in decreased pharmaceutical shelf life in vitro and serious illness or death in vivo.
520 $a Insulin fibril formation has long been studied, due to the protein's significance as a treatment for diabetes mellitus. Lysozyme, on the other hand, has only recently been identified as an amyloidogenic protein, but is structurally well characterized. Unlike insulin and lysozyme, transthyretin is the main amyloid building block for two amyloid diseases that often result in serious injury or premature death.
520 $a In the present study, we use the chaotropic agent guanidine hydrochloride (GdnHCl) to destabilize lysozyme (hen egg white lysozyme), insulin (bovine pancreas insulin), and transthyretin (recombinant human) in order to induce fibrillation. GdnHCl has been shown to interrupt the interactions that allow structural elements in a protein to form. High concentrations can completely denature most proteins.
520 $a In the absence of GdnHCl, lysozyme does not form fibrils on an appreciable time scale. Adding low levels of GdnHCl (2--3 M) brings about a conformation change in the structure and allows the rapid formation of fibrils. Higher levels of GdnHCl (>5M) slow fibril formation by dissolving the nascent fibrils. The results are qualitatively similar for insulin. While fibrils form in the absence of GdnHCl, low levels of GdnHCl (2 M) rapidly increase the rate of fibrillation by dissociating the native hexameric structure of insulin. Again, higher levels of GdnHCl (>5 M) slow and eventually inhibit fibril formation. Transthyretin, unlike insulin and lysozyme, does not form fibrils under any conditions including upon the addition of GdnHCl or urea. The transthyretin mutant G53S/E54D/L55S, a recombinantly produced mutant of wild type human transthyretin, forms fibrils rapidly. The addition of chaotropic agents to the mutant transthyretin species inhibits fibril formation completely. The results here show that different proteins follow different pathways when forming fibrils, and that care must be taken when generalizing fibril formation pathways.
590 $a School code: 0234.
650 4 $a Engineering, Chemical. $3 1018531
650 4 $a Engineering, Biomedical. $3 1017684
650 4 $a Biophysics, General. $3 1019105
690 $a 0542
690 $a 0541
690 $a 0786
710 2 0 $a Tufts University. $3 1017847
773 0 $t Dissertation Abstracts International $g 65-03B.
790 1 0 $a Clark, Eliana De Bernardez, $e advisor
790 $a 0234
791 $a Ph.D.
792 $a 2004
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3124799