Modulation of amyloid self-assembly of ß-amyloid peptide (Aß) and islet amyloid polypeptide (IAPP) via IAPP cross-amyloid interaction surface mimics:
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| Format: | Thesis Book |
| Language: | English |
| Published: |
Aachen
[2018]
|
| Subjects: | |
| Online Access: | Inhaltsverzeichnis Inhaltsverzeichnis |
| Physical Description: | viii, 265 Seiten Illustrationen 21 cm |
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MARC
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| 100 | 1 | |a Malideli, Eleni |d 1986- |e Verfasser |0 (DE-588)1178235963 |4 aut | |
| 245 | 1 | 0 | |a Modulation of amyloid self-assembly of ß-amyloid peptide (Aß) and islet amyloid polypeptide (IAPP) via IAPP cross-amyloid interaction surface mimics |c Eleni Malideli |
| 264 | 1 | |a Aachen |c [2018] | |
| 300 | |a viii, 265 Seiten |b Illustrationen |c 21 cm | ||
| 336 | |b txt |2 rdacontent | ||
| 337 | |b n |2 rdamedia | ||
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| 502 | |b Dissertation |c RWTH Aachen University |d 2018 | ||
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Record in the Search Index
| _version_ | 1804180056442929152 |
|---|---|
| adam_text | INDEX
1
INTRODUCTION
........................................
1
1.1
PROTEIN
FOLDING,
MISFOLDING
AND
AGGREGATION
1
1.1.1
PROTEOSTASIS
NETWORK
(PN)
2
1.1.2
PROTEIN
MISFOLDING
DISEASES
(PMDS)
3
1.2
THE
AMYLOID
STATE
5
1.2.1
STRUCTURAL
CHARACTERISTICS
5
1.2.2
FORMATION
6
1.3
ALZHEIMER
*
S
DISEASE
(AD)
AND
THE
AMYLOID
CASCADE
HYPOTHESIS
8
1.3.1
GENERATION
OF
P-AMYLOID
POLYPEPTIDE
(AP)
BY
THE
P-AMYLOID
PRECURSOR
PROTEIN
(APP)
8
1.3.2
MORPHOLOGICAL
AND
STRUCTURAL
CHARACTERISTICS
OF
AP
AMYLOID
FIBRILS
10
1.4
PROMISING
THERAPEUTIC
STRATEGIES
TO
TREAT
AD
BY
TARGETING
AP
POLYPEPTIDE
12
1.4.1
INHIBITION
OF
AP
PRODUCTION
12
1.4.2
INHIBITION
OF
AP
AGGREGATION
13
1.4.3
CLEARANCE
OF
AP
FROM
THE
BRAIN
16
1.5
TYPE
2
DIABETES
(T2D)
AND
ISLET
AMYLOID
POLYPEPTIDE
(IAPP)
17
1.5.1
GENERATION
AND
STRUCTURAL
PROPERTIES
OF
IAPP
18
1.5.2
MORPHOLOGICAL
AND
STRUCTURAL
CHARACTERISTICS
OF
IAPP
AMYLOID
FIBRILS
19
1.5.3
INHIBITION
OF
IAPP
AMYLOID
SELF-ASSEMBLY
AND
CYTOTOXICITY
21
1.6
CROSS-AMYLOID
INTERACTIONS
22
1.6.1
LINK
BETWEEN
AD
AND
T2D:
MOLECULAR
CROSS-TALK
BETWEEN
AP
AND
IAPP
24
1.7
PREVIOUS
FINDINGS
LEADING
TO
THIS
STUDY
25
1.7.1
AIMS
OF
THIS
STUDY
26
2
MATERIALS
AND
METHODS
28
2.1
MATERIALS
28
2.1.1
PEPTIDES
28
2.1.2
CHEMICALS
.......................................................................................................
28
2.1.3
ASSAY
KITS
30
2.1.4
ASSAY
MATERIALS
30
2.1.5
CELL
CULTURE
GROWTH
FACTORS
30
2.2
METHODS
31
2.2.1
SOLID
PHASE
PEPTIDE
SYNTHESIS
(SPPS)
31
2.2.2
COUPLING
OF
THE
C-TERMINAL
AMINO
ACID
TO
THE
RESIN
AND
SUBSTITUTION
LEVEL
DETERMINATION
32
2.2.3
COUPLING
AND
FMOC-DEPROTECTION
OF
N-METHYL
RESIDUES
AND
ON
N-METHYL
RESIDUES
33
2.2.4
N-TERMINAL
LABELING
OF
PEPTIDES
WITH
FLUORESCEIN
(FLUOS-)
..................................................................
33
2.2.5
KAISER
TEST
.............................................................................................................................................
33
2.2.6
ACETALDEHYDE/CHLORANIL
TEST
.................................................................................................................
34
2.2.7
FINAL
CLEAVAGE
OF
PEPTIDES
FROM
THE
RESIN
..........................................................................................
34
2.2.8
DISULFIDE
BRIDGE
FORMATION
OF
IAPP
......................................................................................................
34
2.2.9
PURIFICATION
AND
CHARACTERIZATION
OF
PEPTIDES
.....................................................................................
35
2.2.10
PEPTIDE
STOCK
SOLUTIONS
........................................................................................................................
36
2.2.11
THIOFLAVIN
T
(THT)
BINDING
ASSAYS
.......................................................................................................
37
2.2.12
TRANSMISSION
ELECTRON
MICROSCOPY
(TEM)
.........................................................................................
38
2.2.13
CELL
CULTURE
............................................................................................................................................
38
2.2.14
FAR-UV
CD
SPECTROSCOPY
.....................................................................................................................
39
2.2.15
ANS
BINDING
FLUORESCENCE
SPECTROSCOPY
............................................................................................
40
2.2.16
FLUORESCENCE
SPECTROSCOPIC
TITRATION
STUDIES
.....................................................................................
40
2.2.17
BICINCHONINIC
ACID
(BCA)
PROTEIN
ASSAY
.............................................................................................
41
2.2.18
SEDIMENTATION
ASSAYS
.........................................................................................................................
42
3
.....
RESULTS
.....................................................................................................................................................................
43
3.1
1
ST
GENERATION
ISMS
........................................................................................................................................
43
3.1.1
DESIGN
CONCEPT
......................................................................................................................................
43
3.1.2
STUDIES
ON
13-61
AND
SPG-GI
..............................................................................................................
44
3.1.3
INTERACTIONS
AND
EFFECTS
OF
1
ST
GENERATIONS
ISMS
ON
AP42
FIBRILLOGENESIS,
CYTOTOXICITY
AND
AP42-
MEDIATED
CROSS-SEEDING
OF
IAPP
...........................................................................................................................
48
3.1.4
MECHANISTIC
STUDIES
OF
1
81
GENERATION
ISMS
........................................................................................
51
3.2
2
ND
GENERATION
ISMS
.......................................................................................................................................
59
3.2.1
ISMS
CONTAINING
MIXTURES
OF
NORLEUCINE
AND
ARGININE
IN
IAPP
(19-21)
REGION
(NLEXRY-GI)
...........
59
3.2.2
ISMS
CONTAINING
MIXTURES
OF
LEUCINE
AND
ARGININE
IN
IAPP
(19-21)
REGION
(LXRY-GI)
......................
87
3.2.3
ISMS
CONTAINING
MIXTURES
OF
LEUCINE
AND
THREONINE
IN
IAPP
(19-21)
REGION
(LXTY-GI)
................
104
3.3
MODIFICATION
CHANGES
AND
SEQUENCE
TRUNCATION
OF
L3-GI
,
A
POTENT
INHIBITOR
OF
AP40(42)
AND
IAPP
AMYLOID
SELF-ASSEMBLY
.............................................................................................................................................................
119
3.3.1
ALA
SUBSTITUTIONS
IN
HOT-SPOT
RESIDUES
OF
L3-GI
................................................................................119
3.3.2
INTRODUCTION
OF
N-METHYLATIONS
IN
SPECIFIC
AMIDE
BONDS
OF
L3-GI
..................................................
138
3.3.3
TRUNCATION
OF
THE
N-TERMINAL
PART
OF
L3-GI
.......................................................................................152
4
.....
DISCUSSION
.............................................................................................................................................................
165
4.1
1
ST
GENERATION
ISMS
.....................................................................................................................................165
4.2
2
ND
GENERATION
ISMS
....................................................................................................................................
168
VII
4.3
MODIFICATION
CHANGES
AND
SEQUENCE
TRUNCATION
OF
L3-GI,
A
POTENT
INHIBITOR
OF
A04O(42)
AND
IAPP
AMYLOID
SELF-ASSEMBLY
174
5
REFERENCES
183
6
LIST
OF
FIGURES
197
7
LIST
OF
TABLES
202
8
ABBREVIATIONS
.................................................................................
204
9
APPENDICES
...................................................................................................................................................
209
10..
.
CURRICULUM
VITAE
263
11..
.
ACKNOWLEDGEMENTS
..............................................
264
12..
.
DECLARATION
265
VIII
|
| any_adam_object | 1 |
| author | Malideli, Eleni 1986- |
| author_GND | (DE-588)1178235963 |
| author_facet | Malideli, Eleni 1986- |
| author_role | aut |
| author_sort | Malideli, Eleni 1986- |
| author_variant | e m em |
| building | Verbundindex |
| bvnumber | BV045896187 |
| ctrlnum | (OCoLC)1104933911 (DE-599)DNB1183845626 |
| discipline | Biologie Medizin |
| format | Thesis Book |
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| genre | (DE-588)4113937-9 Hochschulschrift gnd-content |
| genre_facet | Hochschulschrift |
| id | DE-604.BV045896187 |
| illustrated | Illustrated |
| indexdate | 2024-07-10T08:29:41Z |
| institution | BVB |
| language | English |
| oai_aleph_id | oai:aleph.bib-bvb.de:BVB01-031279109 |
| oclc_num | 1104933911 |
| open_access_boolean | |
| owner | DE-355 DE-BY-UBR |
| owner_facet | DE-355 DE-BY-UBR |
| physical | viii, 265 Seiten Illustrationen 21 cm |
| publishDate | 2018 |
| publishDateSearch | 2018 |
| publishDateSort | 2018 |
| record_format | marc |
| spelling | Malideli, Eleni 1986- Verfasser (DE-588)1178235963 aut Modulation of amyloid self-assembly of ß-amyloid peptide (Aß) and islet amyloid polypeptide (IAPP) via IAPP cross-amyloid interaction surface mimics Eleni Malideli Aachen [2018] viii, 265 Seiten Illustrationen 21 cm txt rdacontent n rdamedia nc rdacarrier Dissertation RWTH Aachen University 2018 (DE-588)4113937-9 Hochschulschrift gnd-content B:DE-101 application/pdf http://d-nb.info/1183845626/04 Inhaltsverzeichnis DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=031279109&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Malideli, Eleni 1986- Modulation of amyloid self-assembly of ß-amyloid peptide (Aß) and islet amyloid polypeptide (IAPP) via IAPP cross-amyloid interaction surface mimics |
| subject_GND | (DE-588)4113937-9 |
| title | Modulation of amyloid self-assembly of ß-amyloid peptide (Aß) and islet amyloid polypeptide (IAPP) via IAPP cross-amyloid interaction surface mimics |
| title_auth | Modulation of amyloid self-assembly of ß-amyloid peptide (Aß) and islet amyloid polypeptide (IAPP) via IAPP cross-amyloid interaction surface mimics |
| title_exact_search | Modulation of amyloid self-assembly of ß-amyloid peptide (Aß) and islet amyloid polypeptide (IAPP) via IAPP cross-amyloid interaction surface mimics |
| title_full | Modulation of amyloid self-assembly of ß-amyloid peptide (Aß) and islet amyloid polypeptide (IAPP) via IAPP cross-amyloid interaction surface mimics Eleni Malideli |
| title_fullStr | Modulation of amyloid self-assembly of ß-amyloid peptide (Aß) and islet amyloid polypeptide (IAPP) via IAPP cross-amyloid interaction surface mimics Eleni Malideli |
| title_full_unstemmed | Modulation of amyloid self-assembly of ß-amyloid peptide (Aß) and islet amyloid polypeptide (IAPP) via IAPP cross-amyloid interaction surface mimics Eleni Malideli |
| title_short | Modulation of amyloid self-assembly of ß-amyloid peptide (Aß) and islet amyloid polypeptide (IAPP) via IAPP cross-amyloid interaction surface mimics |
| title_sort | modulation of amyloid self assembly of ß amyloid peptide aß and islet amyloid polypeptide iapp via iapp cross amyloid interaction surface mimics |
| topic_facet | Hochschulschrift |
| url | http://d-nb.info/1183845626/04 http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=031279109&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
| work_keys_str_mv | AT malidelieleni modulationofamyloidselfassemblyofßamyloidpeptideaßandisletamyloidpolypeptideiappviaiappcrossamyloidinteractionsurfacemimics |
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