Peptides to target serpin-serine protease interactions:
Gespeichert in:
| 1. Verfasser: | |
|---|---|
| Format: | Abschlussarbeit Elektronisch Software E-Book |
| Sprache: | English |
| Veröffentlicht: |
Leipzig
2016
|
| Schlagworte: | |
| Online-Zugang: | Inhaltsverzeichnis Inhaltsverzeichnis |
| Beschreibung: | 1 CD-ROM (197 Seiten) Illustrationen 12 cm |
Internformat
MARC
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| 100 | 1 | |a Jendrny, Cathleen |d 1986- |e Verfasser |0 (DE-588)1147419167 |4 aut | |
| 245 | 1 | 0 | |a Peptides to target serpin-serine protease interactions |c vorgelegt von Apothekerin und Diplom-Pharmazeutin Cathleen Jendrny |
| 264 | 1 | |a Leipzig |c 2016 | |
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| 502 | |b Dissertation |c Fakultät für Biowissenschaften, Pharmazie und Psychologie der Universität Leipzig |d 2016 | ||
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Datensatz im Suchindex
| _version_ | 1804180473108234240 |
|---|---|
| adam_text | T
ABLE
OF
C
ONTENTS
A
BBREVIATIONS
6
B
IBLIOGRAPHISCHE
D
ARSTELLUNG
10
Z
USAMMENFASSUNG
11
S
UMMARY
18
1 S
ERINE
P
ROTEASES
AND
T
HEIR
N
ATURAL
I
NHIBITORS
OF
THE
S
ERPIN
F
AMILY
24
1.1 S
ERINE
P
ROTEASES
25
1.1.1 ORGANIZATION AND DISTRIBUTION 25
1.1.2 CATALYTIC TRIAD AND MECHANISM OF ACTION 25
1.1.3 PRIMARY SPECIFICITY 27
1.1.4 BIOLOGICAL FUNCTIONS 28
1.2 T
HE
F
AMILY
OF
K
ALLIKREIN
-R
ELATED
P
EPTIDASES
28
1.2.1 HOMOLOGY, STRUCTURE, AND ACTIVATION 28
1.2.2 SUBSTRATE SPECIFICITY 30
1.2.3 TISSUE EXPRESSION AND BIOLOGICAL FUNCTIONS 30
1.2.4 KLKS IN CANCER AND THEIR POTENTIAL AS CANCER BIOMARKERS 31
1.3 N
ATURAL
I
NHIBITORS
OF
S
ERINE
P
ROTEASES
32
1.3.1 CANONICAL AND NON-CANONICAL SERINE PROTEASE INHIBITORS 32
1.3.2 SERPINS 32
1.4 A
IMS
OF
THE
T
HESIS
34
1.5 A
CKNOWLEDGEMENTS
36
1.6 R
EFERENCES
36
2 P
EPTIDES
AS
M
ODULATORS
OF
S
ERPIN
A
CTION
43
2.1 S
UMMARY
44
2.2 T
HE
S
ERPIN
F
AMILY
: S
TRUCTURAL
C
HARACTERISTICS
AND
F
UNCTIONAL
D
IVERSITY
45
2.2.1 STRUCTURAL CHARACTERISTICS AND MECHANISM O F FUNCTION 45
2.2.2 SERPINS IN PHYSIOLOGICAL AND PATHOLOGICAL PROCESSES 46
2.2.3 NATURAL MODULATION OF SERPIN ACTION AND SPECIFICITY 47
2.3 P
EPTIDES
AS
M
ODULATORS
OF
S
ERPIN
F
UNCTIONS
AND
D
YSFUNCTIONS
48
2.3.1 PEPTIDES INHIBITING SERPIN ACTION 49
2.3.2 PEPTIDES INHIBITING SERPIN POLYMERIZATION 52
2.3.3 PEPTIDES MIMICKING SERPIN ACTION 54
2.4 C
ONCLUSION
56
2.5 A
CKNOWLEDGEMENTS
56
2.6 R
EFERENCES
56
3 I
NHIBITION
OF
K
ALLIKREIN
-R
ELATED
P
EPTIDASES
7
AND
5
BY
G
RAFTING
S
ERPIN
R
EACTIVE
-C
ENTER
L
OOP
S
EQUENCES
ONTO
S
UNFLOWER
T
RYPSIN
I
NHIBITOR
-1 (SFTI-1) 65
3.1 S
UMMARY
66
3.2 I
NTRODUCTION
67
3.3 E
XPERIMENTAL
P
ROCEDURES
68
3.3.1 MATERIAL 68
3.3.2 PEPTIDE SYNTHESIS 69
3.3.3 KLK7 ACTIVATION 70
3.3.4 KLK7 DIGESTION OF SUBSTRATE PEPTIDES 70
3.3.5 ENZYME KINETICS 71
3.3.6 KLK7 AND KLK5 INHIBITION ASSAYS 71
3.3.7 IC5O AND K; DETERMINATION 72
3.3.8 CD SPECTROSCOPY 72
3.4 R
ESULTS
73
3.4.1 RCL-DERIVED KLK7 SUBSTRATES 73
3.4.2 DESIGN O F RCL-SFTI PEPTIDES AND INHIBITION OF KLK7 AND KLK5 74
3.5 D
ISCUSSION
77
3.6 C
ONCLUSION
81
3.7 A
CKNOWLEDGEMENTS
82
3.8 R
EFERENCES
82
3.9 S
UPPORTING
I
NFORMATION
86
3.10 A
PPENDIX
: R
ETRO
-I
NVERSO
SFTI P
EPTIDES
88
3.10.1 INTRODUCTION 88
3.10.2 EXPERIMENTAL PROCEDURES 89
3.10.3 RESULTS 90
3.10.4 DISCUSSION 93
3.10.5 CONCLUSION 95
3.10.6 ACKNOWLEDGEMENTS 95
3.10.7 REFERENCES 95
4 S
ERPIN
-S
UNFLOWER
T
RYPSIN
I
NHIBITOR
-1
(SFTI-1)
H
YBRID
P
EPTIDES
AS
T
OOLS
: I
DENTIFICATION
OF
AN
I
NTERACTION
B
ETWEEN
P
ROTEIN
C
I
NHIBITOR
(PCI)
AND
K
ALLIKREIN
-R
ELATED
P
EPTIDASE
4 (KLK4) 99
4.1 S
UMMARY
100
4.2 I
NTRODUCTION
101
4.3 E
XPERIMENTAL
P
ROCEDURES
102
4.3.1 MATERIAL 102
4.3.2 KLK4 ACTIVATION 103
4.3.3 ENZYME KINETICS OF BOC-VPR-AMC CLEAVAGE BY KLK4 103
4.3.4 KLK4 INHIBITION ASSAY 104
4.3.5 COMPLEX FORMATION ASSAY 104
4.3.6 SDS-PAGE 105
4.3.7 VISUALIZATION OF PROTEIN BANDS ON POLYACRYLAMIDE GELS AND
QUANTIFICATION OF BAND INTENSITIES 105
4.3.8 IDENTIFICATION OF PCI CLEAVAGE SITES BY MALDI-TOF MS 105
4.4 R
ESULTS
106
4.4.1 KLK4 INHIBITION BY RCL-SFTI PEPTIDES 106
4.4.2 STUDIES ON THE INTERACTION OF KLK4 AND PCI 108
4.4.3 IDENTIFICATION OF PCI CLEAVAGE SITES 109
4.5 D
ISCUSSION
111
4.6 C
ONCLUSION
114
4.7 A
CKNOWLEDGEMENTS
115
4.8 R
EFERENCES
115
5 R
ATIONAL
D
ESIGN
OF
P
EPTIDE
I
NHIBITORS
OF
THE
P
ROTEIN
-P
ROTEIN
I
NTERACTION
OF
P
ROTEIN
Z-D
EPENDENT
P
ROTEASE
I
NHIBITOR
AND
I
TS
C
OFACTOR
P
ROTEIN
Z 120
5.1 S
UMMARY
121
5.2 I
NTRODUCTION
122
5.3 E
XPERIMENTAL
P
ROCEDURES
124
5.3.1 MATERIAL 124
5.3.2 SOLID-PHASE PEPTIDE SYNTHESIS 125
5.3.3 CIRCULAR DICHROISM SPECTROSCOPY 126
5.4 R
ESULTS
127
5.4.1 PEPTIDE DESIGN AND PEPTIDE SYNTHESIS 127
5.4.2 CIRCULAR DICHROISM SPECTROSCOPY 131
5.4.3 BIOLOGICAL ACTIVITY 134
5.5 D
ISCUSSION
134
5.6 C
ONCLUSION
139
5.7 A
CKNOWLEDGEMENTS
139
5.8 R
EFERENCES
140
6 S
TUDYING
THE
B
INDING
S
ITE
OF
A
P
EPTIDE
I
NHIBITOR
OF
THE
I
NTERACTION
OF
P
ROTEIN
Z-D
EPENDENT
P
ROTEASE
I
NHIBITOR
(ZPI)
AND
P
ROTEIN
Z (PZ)
BY
P
HOTO
-C
ROSSLINKING
AND
M
ASS
S
PECTROMETRY
144
6.1 S
UMMARY
145
6.2 I
NTRODUCTION
146
6.3 E
XPERIMENTAL
P
ROCEDURES
148
6.3.1 MATERIAL 148
6.3.2 SOLID-PHASE PEPTIDE SYNTHESIS 149
6.3.3 PHOTO-CROSSLINKING 150
6.3.4 COMPETITION PHOTO-CROSSLINKING EXPERIMENT 151
6.3.5 AFFINITY PURIFICATION 151
6.3.6 CLEAVAGE OF N-LINKED OLIGOSACCHARIDES 152
6.3.7 DIGESTION WITH ENDOPROTEINASES 152
6.3.8 SDS-PAGE 153
6.3.9 TRICINE-SDS-PAGE 154
6.3.10 WESTERN BLOT 154
6.3.11 MALDI-TOF MS 155
6.3.12 DETERMINATION O F ZPI CLEAVAGE FRAGMENTS 155
6.4 R
ESULTS
156
6.4.1 PEPTIDE MODIFICATION WITH BPA AND BIOTIN 156
6.4.2 IDENTIFICATION OF CROSSLINKED ZPI-PEPTIDE COMPLEXES 158
6.4.3 ENZYMATIC DIGESTION OF ZPI-PEPTIDE COMPLEXES BY ENDOPROTEINASES
160
6.4.4 AFFINITY PURIFICATION 162
6.4.5 ANALYSIS OF POTENTIAL ZPI-PEPTIDE BINDING REGIONS 163
6.5 D
ISCUSSION
167
6.6 C
ONCLUSION
173
6.7 A
CKNOWLEDGEMENT
174
6.8 R
EFERENCES
174
6.9 S
UPPORTING
I
NFORMATION
178
P
UBLICATIONS
AND
P
RESENTATIONS
186
C
URRICULUM
V
ITAE
188
S
ELBSTSTAENDIGKEITSERKLAERUNG
189
D
ANKSAGUNG
190
A
UTHOR
C
ONTRIBUTION
192
|
| any_adam_object | 1 |
| author | Jendrny, Cathleen 1986- |
| author_GND | (DE-588)1147419167 |
| author_facet | Jendrny, Cathleen 1986- |
| author_role | aut |
| author_sort | Jendrny, Cathleen 1986- |
| author_variant | c j cj |
| building | Verbundindex |
| bvnumber | BV046141030 |
| ctrlnum | (OCoLC)1119006147 (DE-599)DNB1147707685 |
| discipline | Biologie |
| format | Thesis Electronic Software eBook |
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| illustrated | Not Illustrated |
| indexdate | 2024-07-10T08:36:19Z |
| institution | BVB |
| language | English |
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| physical | 1 CD-ROM (197 Seiten) Illustrationen 12 cm |
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| spelling | Jendrny, Cathleen 1986- Verfasser (DE-588)1147419167 aut Peptides to target serpin-serine protease interactions vorgelegt von Apothekerin und Diplom-Pharmazeutin Cathleen Jendrny Leipzig 2016 1 CD-ROM (197 Seiten) Illustrationen 12 cm txt rdacontent c rdamedia cd rdacarrier Dissertation Fakultät für Biowissenschaften, Pharmazie und Psychologie der Universität Leipzig 2016 (DE-588)4113937-9 Hochschulschrift gnd-content (DE-588)4139307-7 CD-ROM gnd-carrier B:DE-101 application/pdf http://d-nb.info/1147707685/04 Inhaltsverzeichnis DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=031521271&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis Textdatei PDF |
| spellingShingle | Jendrny, Cathleen 1986- Peptides to target serpin-serine protease interactions |
| subject_GND | (DE-588)4113937-9 (DE-588)4139307-7 |
| title | Peptides to target serpin-serine protease interactions |
| title_auth | Peptides to target serpin-serine protease interactions |
| title_exact_search | Peptides to target serpin-serine protease interactions |
| title_full | Peptides to target serpin-serine protease interactions vorgelegt von Apothekerin und Diplom-Pharmazeutin Cathleen Jendrny |
| title_fullStr | Peptides to target serpin-serine protease interactions vorgelegt von Apothekerin und Diplom-Pharmazeutin Cathleen Jendrny |
| title_full_unstemmed | Peptides to target serpin-serine protease interactions vorgelegt von Apothekerin und Diplom-Pharmazeutin Cathleen Jendrny |
| title_short | Peptides to target serpin-serine protease interactions |
| title_sort | peptides to target serpin serine protease interactions |
| topic_facet | Hochschulschrift CD-ROM |
| url | http://d-nb.info/1147707685/04 http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=031521271&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
| work_keys_str_mv | AT jendrnycathleen peptidestotargetserpinserineproteaseinteractions |
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