Tools

LEADER 04108cam a2200517Ii 4500

001 ocn847755818;

003 OCoLC;

005 20141212054338.0;

006 m o d ;

007 cr bn|||||||||;

008 130612s2012 ncua obm 000 0 eng d;

035 a| (Sirsi) o847755818;

035 a| (OCoLC)847755818;

049 a| EREE;

090 a| RC523;

100 1 a| Gade, Sunitha.?| UNAUTHORIZED;

245 10 a| Cu²⁺ binding to A[beta] peptides :b| detailed heat capacity studies provide structural insight into complex formation /c| by Sunitha Gade.;

260 a| [Greenville, N.C.] :b| East Carolina University,c| 2012.;

300 a| 72 pages :b| illustrations (some color), digital, PDF file;

336 a| textb| txt2| rdacontent;

337 a| computerb| c2| rdamedia;

338 a| online resourceb| cr2| rdacarrier;

538 a| System requirements: Adobe Reader.;

538 a| Mode of access: World Wide Web.;

502 b| M.S.c| East Carolina Universityd| 2012.;

500 a| Presented to the faculty of the Department of Chemistry.;

500 a| Advisor: Anne Spuches.;

500 a| Title from PDF t.p. (viewed July 24, 2013).;

520 3 a| Alzheimer's disease (AD), an irreversible, progressive and devastating neurodegenerative disease, is the most common cause of dementia. It is characterized by the extracellular amyloid plaques and the intracellular neurofibrillary tangles. Amyloid plaques are majorly constituted of A[beta] peptides, which are cleaved from the membrane bound amyloid precursor protein (APP). A[beta] peptides consist of either 40 or 42 amino acid residues. Elevated concentrations of copper, zinc, and iron have been measured in amyloid plaques and recent in vitro studies have shown that zinc and copper ions promote the aggregation of these peptides. Furthermore, it was found that high affinity metal ion chelators can be used in the dissolution of aggregated A[beta] peptides. Taken together, these studies show the important role metal ions play in AD. In vitro studies have shown that aggregation of human A[beta] peptides increases due to the presence of Cu, but this effect is much less profound for rat A[beta] peptides. Previous studies indicate that Cu²⁺ binding occurs within the first 16 amino acid residues of the full length A[beta] peptides. Our lab has investigated the thermodynamics of Cu²⁺ binding to A[beta]16, A[beta]28 and three variant peptides using isothermal titration calorimetry (ITC) and ACES buffer as a weak competing ligand. In this study, the binding of Cu²⁺ to A[beta]16 was studied at three different concentrations of ACES buffer (20mM, 50mM, and 100mM). Buffer independent binding constants (K) are then extracted to test for ternary complex formation. According to the thermodynamic studies of Cu²⁺ binding to A[beta]28 and A[beta]28 mutants, a model was proposed, which was further tested by obtaining the heat capacity ([delta]C[subscript]p) data for Cu²⁺ binding to A[beta]16 A[beta]28 and A[beta]28 mutants. In addition, heat capacity ([delta]C[subscript]p) data for Cu²⁺ binding to Rat A[beta]28 is obtained and compared to human A[beta]28. Taken together, this data will be used to shed light on why the rat peptides do not form fibrils.;

504 a| Includes bibliographical references.;

650 0 a| Alzheimer's disease.=| ^A12721;

650 0 a| Amyloid beta-protein.=| ^A692443;

650 0 a| Amyloid beta-protein precursor.=| ^A867936;

650 0 a| Metal ions.=| ^A45006;

653 a| Chemistry;

653 a| Inorganic chemistry;

700 1 a| Spuches, Anne M.?| UNAUTHORIZED;

710 2 a| East Carolina University.b| Department of Chemistry.?| UNAUTHORIZED;

856 40 z| Access via ScholarShipu| http://hdl.handle.net/10342/1814;

949 o| jgml;

994 a| C0b| ERE;

596 a| 1 4;

998 a| 3321497;

999 a| CLICK ON WEB ADDRESSw| ASISc| 1i| 3321497-1001l| JNETm| JOYNERr| Ys| Yt| JNE3ETDu| 6/12/2013x| ETDz| JERESOURCE;

999 a| CLICK ON WEB ADDRESSw| ASISc| 1i| 3321497-2001l| HSLELECm| HSLr| Ys| Yt| HEETDu| 6/12/2013x| ETDz| HERESOURCE;

Cu²⁺ binding to A[beta] peptides : detailed heat capacity studies provide structural insight into complex formation / by Sunitha Gade.

Author/creator	Gade, Sunitha
Other author	Spuches, Anne M.
Other author	East Carolina University. Department of Chemistry.
Format	Theses and dissertations
Publication Info	[Greenville, N.C.] : East Carolina University, 2012.
Description	72 pages : illustrations (some color), digital, PDF file
Supplemental Content	Access via ScholarShip
Subjects	Alzheimer's disease. Amyloid beta-protein. Amyloid beta-protein precursor. Metal ions.

Summary	Alzheimer's disease (AD), an irreversible, progressive and devastating neurodegenerative disease, is the most common cause of dementia. It is characterized by the extracellular amyloid plaques and the intracellular neurofibrillary tangles. Amyloid plaques are majorly constituted of A[beta] peptides, which are cleaved from the membrane bound amyloid precursor protein (APP). A[beta] peptides consist of either 40 or 42 amino acid residues. Elevated concentrations of copper, zinc, and iron have been measured in amyloid plaques and recent in vitro studies have shown that zinc and copper ions promote the aggregation of these peptides. Furthermore, it was found that high affinity metal ion chelators can be used in the dissolution of aggregated A[beta] peptides. Taken together, these studies show the important role metal ions play in AD. In vitro studies have shown that aggregation of human A[beta] peptides increases due to the presence of Cu, but this effect is much less profound for rat A[beta] peptides. Previous studies indicate that Cu²⁺ binding occurs within the first 16 amino acid residues of the full length A[beta] peptides. Our lab has investigated the thermodynamics of Cu²⁺ binding to A[beta]16, A[beta]28 and three variant peptides using isothermal titration calorimetry (ITC) and ACES buffer as a weak competing ligand. In this study, the binding of Cu²⁺ to A[beta]16 was studied at three different concentrations of ACES buffer (20mM, 50mM, and 100mM). Buffer independent binding constants (K) are then extracted to test for ternary complex formation. According to the thermodynamic studies of Cu²⁺ binding to A[beta]28 and A[beta]28 mutants, a model was proposed, which was further tested by obtaining the heat capacity ([delta]C[subscript]p) data for Cu²⁺ binding to A[beta]16 A[beta]28 and A[beta]28 mutants. In addition, heat capacity ([delta]C[subscript]p) data for Cu²⁺ binding to Rat A[beta]28 is obtained and compared to human A[beta]28. Taken together, this data will be used to shed light on why the rat peptides do not form fibrils.
General note	Presented to the faculty of the Department of Chemistry.
General note	Advisor: Anne Spuches.
General note	Title from PDF t.p. (viewed July 24, 2013).
Dissertation note	M.S. East Carolina University 2012.
Bibliography note	Includes bibliographical references.
Technical details	System requirements: Adobe Reader.
Technical details	Mode of access: World Wide Web.

Availability

Library	Location	Call Number	Status	Item Actions
	Electronic Resources	Access Content Online	✔ Available

Cu²⁺ binding to A[beta] peptides : detailed heat capacity studies provide structural insight into complex formation / by Sunitha Gade.

Click here for more information about this title

Availability