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Sequence determinants and inhibition...

Kim, Woojin.

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Sequence determinants and inhibition of the aggregation of the Alzheimer's Abeta peptide.

Record Type:	Language materials, printed : Monograph/item
Title/Author:	Sequence determinants and inhibition of the aggregation of the Alzheimer's Abeta peptide./
Author:	Kim, Woojin.
Description:	151 p.
Notes:	Adviser: Michael H. Hecht.
Contained By:	Dissertation Abstracts International68-01B.
Subject:	Chemistry, Biochemistry. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3250034

Sequence determinants and inhibition of the aggregation of the Alzheimer's Abeta peptide.
Kim, Woojin.

Sequence determinants and inhibition of the aggregation of the Alzheimer's Abeta peptide. - 151 p.

Adviser: Michael H. Hecht.

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

Studies of Alzheimer's disease reveal that aggregation of the amyloid-beta (Abeta) peptides play a crucial role in the pathogenesis of this disease. In this thesis, the sequence determinants of the aggregation of Abeta peptides were investigated by using a fusion of Abeta to green fluorescent protein (GFP). Wurth, Guimard, and Hecht showed previously that GFP fusions to wild type Aa aggregate and exhibit white phenotypes, whereas soluble mutants of the Abeta. GFP fusion exhibit green phenotypes. Screening the solubility of (Abeta mutant)-GFP fusions and subsequent sequence analysis elucidated the sequence determinants of the aggregation of Abeta.Subjects--Topical Terms:

1017722
Chemistry, Biochemistry.

Sequence determinants and inhibition of the aggregation of the Alzheimer's Abeta peptide.
LDR:02703nam 2200301 a 45 001 954204
005 20110621
008 110622s2007 eng d
035 $a (UMI)AAI3250034
035 $a AAI3250034
040 $a UMI $c UMI
100 1 $a Kim, Woojin. $3 1277677
245 1 0 $a Sequence determinants and inhibition of the aggregation of the Alzheimer's Abeta peptide.
300 $a 151 p.
500 $a Adviser: Michael H. Hecht.
500 $a Source: Dissertation Abstracts International, Volume: 68-01, Section: B, page: 0274.
502 $a Thesis (Ph.D.)--Princeton University, 2007.
520 $a Studies of Alzheimer's disease reveal that aggregation of the amyloid-beta (Abeta) peptides play a crucial role in the pathogenesis of this disease. In this thesis, the sequence determinants of the aggregation of Abeta peptides were investigated by using a fusion of Abeta to green fluorescent protein (GFP). Wurth, Guimard, and Hecht showed previously that GFP fusions to wild type Aa aggregate and exhibit white phenotypes, whereas soluble mutants of the Abeta. GFP fusion exhibit green phenotypes. Screening the solubility of (Abeta mutant)-GFP fusions and subsequent sequence analysis elucidated the sequence determinants of the aggregation of Abeta.
520 $a Results presented in this thesis showed that mutating Ile41 and Ala42 to hydrophilic residues increases solubility, while mutating the same residues to hydrophobic residues enhances the aggregation propensity. This result suggests that the enhanced aggregation propensity of Abeta42 relative to Abeta40 results from the hydrophobic nature of Ile41 and Ala42 residues (Chapter 2). Fusions of GFP to Abeta mutants containing 8&sim;12 mutations of hydrophobic residues to other hydrophobic residues produced white phenotypes, suggesting that generic hydrophobicity (rather than specific nonpolar side chains) at key positions is sufficient to promote aggregation of Abeta42 (Chapter 3). Sequence analysis of Abeta40 mutants with enhanced aggregation propensities indicated that an overall increase in hydrophobicity caused increased aggregation (Chapter 4).
520 $a Finally, a library of compounds was screened using the Abeta-GFP fusion to identify drug leads that inhibit aggregation of Abeta (Chapter 5). The inhibitory activities of the molecules screened using the Abeta-GFP fusion were confirmed using a series of biophysical techniques.
590 $a School code: 0181.
650 4 $a Chemistry, Biochemistry. $3 1017722
650 4 $a Chemistry, Pharmaceutical. $3 550957
650 4 $a Health Sciences, Pathology. $3 1017854
690 $a 0487
690 $a 0491
690 $a 0571
710 2 $a Princeton University. $3 645579
773 0 $t Dissertation Abstracts International $g 68-01B.
790 $a 0181
790 1 0 $a Hecht, Michael H., $e advisor
791 $a Ph.D.
792 $a 2007
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3250034