Novel ligands for protease-activated receptor 2: synthesis and biological investigation = Neuartige Liganden für den Protease-aktivierten Rezeptor 2
Saved in:
| Main Author: | |
|---|---|
| Format: | Thesis Book |
| Language: | English |
| Published: |
Erlangen ; Nürnberg
[2019]
|
| Subjects: | |
| Online Access: | Inhaltsverzeichnis Inhaltsverzeichnis |
| Physical Description: | 356 Seiten Illustrationen, Diagramme 21 cm |
Staff View
MARC
| LEADER | 00000nam a2200000 c 4500 | ||
|---|---|---|---|
| 001 | BV046227807 | ||
| 003 | DE-604 | ||
| 005 | 20200427 | ||
| 007 | t | ||
| 008 | 191104s2019 gw a||| m||| 00||| eng d | ||
| 016 | 7 | |a 1197761950 |2 DE-101 | |
| 020 | |c Broschur | ||
| 035 | |a (OCoLC)1126552535 | ||
| 035 | |a (DE-599)DNB1197761950 | ||
| 040 | |a DE-604 |b ger |e rda | ||
| 041 | 0 | |a eng | |
| 044 | |a gw |c XA-DE | ||
| 049 | |a DE-29 |a DE-29T |a DE-355 | ||
| 084 | |a 540 |2 sdnb | ||
| 084 | |a 570 |2 sdnb | ||
| 100 | 1 | |a Klösel, Ilona |d 1990- |e Verfasser |0 (DE-588)119817160X |4 aut | |
| 245 | 1 | 0 | |a Novel ligands for protease-activated receptor 2 |b synthesis and biological investigation = Neuartige Liganden für den Protease-aktivierten Rezeptor 2 |c vorgelegt von Ilona Klösel |
| 246 | 1 | 3 | |a Neuartige Liganden für den Protease-aktivierten Rezeptor 2 |
| 246 | 1 | 1 | |a Neuartige Liganden für den Protease-aktivierten Rezeptor 2 |
| 264 | 1 | |a Erlangen ; Nürnberg |c [2019] | |
| 300 | |a 356 Seiten |b Illustrationen, Diagramme |c 21 cm | ||
| 336 | |b txt |2 rdacontent | ||
| 337 | |b n |2 rdamedia | ||
| 338 | |b nc |2 rdacarrier | ||
| 502 | |b Dissertation |c Friedrich-Alexander-Universität Erlangen-Nürnberg |d 2019 | ||
| 650 | 0 | 7 | |a Ligand |0 (DE-588)4035711-9 |2 gnd |9 rswk-swf |
| 650 | 0 | 7 | |a G-Protein gekoppelter Rezeptor |0 (DE-588)7723480-7 |2 gnd |9 rswk-swf |
| 655 | 7 | |0 (DE-588)4113937-9 |a Hochschulschrift |2 gnd-content | |
| 689 | 0 | 0 | |a G-Protein gekoppelter Rezeptor |0 (DE-588)7723480-7 |D s |
| 689 | 0 | 1 | |a Ligand |0 (DE-588)4035711-9 |D s |
| 689 | 0 | |5 DE-604 | |
| 856 | 4 | 2 | |m B:DE-101 |q application/pdf |u https://d-nb.info/1197761950/04 |3 Inhaltsverzeichnis |
| 856 | 4 | 2 | |m DNB Datenaustausch |q application/pdf |u http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=031606338&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |3 Inhaltsverzeichnis |
| 999 | |a oai:aleph.bib-bvb.de:BVB01-031606338 | ||
Record in the Search Index
| _version_ | 1804180634841645056 |
|---|---|
| adam_text | TABLE
OF
CONTENTS
TABLE
OF
CONTENTS
1.
PROTEASE-ACTIVATED
RECEPTORS
...........................................................................................................
1
1.1.
MECHANISMS
OF
ACTIVATION
..............................................................................................................
2
1.2.
SIGNALING
PATHWAYS
AND
DESENSITIZATION
........................................................................................
4
1.3.
CONTRIBUTION
TO
PHYSIOLOGY
AND
DISEASE.........................................................................................
5
1.4.
LIGAND
DEVELOPMENT
FOR
PROTEASE-ACTIVATED
RECEPTOR
2
...............................................................
7
2.
OBJECTIVE
OF
THE
THESIS
....................................................................................................................
12
3.
PEPTIDIC
PAR2
LIGANDS
.......................................................................................................................
15
3.1.
BIOLOGICAL
EVALUATION
....................................................................................................................
16
3.2.
G
Q
PROTEIN
ACTIVATION
..................................................................................................................
17
3.3.
RECRUITMENT
OF
P-ARRESTIN-2
.........................................................................................................
18
3.4.
CONCLUSIONS
...................................................................................................................................
20
4.
PEPTIDOMIMETICS
WITH
SPIROCYCLIC
C-TERMINUS
.............................................................................
21
4.1.
SYNTHESIS
STRATEGY
.........................................................................................................................
21
4.2.
NMR
STUDIES
.................................................................................................................................
26
4.3.
BIOLOGICAL
EVALUATION
....................................................................................................................
28
4.4.
CONCLUSION
....................................................................................................................................
31
5.
SMALL
PEPTIDOMIMETIC
PAR2
LIGANDS
............................................................................................
33
5.1.
SYNTHESIS
STRATEGY
.........................................................................................................................
33
5.2.
BIOLOGICAL
EVALUATION
....................................................................................................................
35
5.3.
CONCLUSION
....................................................................................................................................
39
6.
NON-PEPTIDIC
PAR2
LIGANDS
.............................................................................................................
40
6.1.
ADDRESSING
THE
LIPOPHILIC
POCKET
.................................................................................................
40
6.2.
SUBSTITUTED
BENZAMIDE
DERIVATIVES
.............................................................................................
40
6.2.1.
SYNTHESIS
STRATEGY
.................................................................................................................
40
6.2.2.
BIOLOGICAL
EVALUATION
............................................................................................................
42
6.2.3.
CONCLUSION
............................................................................................................................
43
6.3.
HOMOLOGOUS
SERIES
.......................................................................................................................
44
6.3.1.
SYNTHESIS
..............................................................................................................................
44
6.3.2.
BIOLOGICAL
EVALUATION
...........................................................................................................
45
6.3.3.
CONCLUSION
...........................................................................................................................
47
6.4.
IK109-DERIVATIVES
..........................................................................................................................
47
6.4.1.
SYNTHESIS...............................................................................................................................
49
6.4.2.
BIOLOGICAL
EVALUATION
.............................................................................................................
51
6.4.3.
CONCLUSION
............................................................................................................................
56
6.5.
PEPTOID
DERIVATIVES
.......................................................................................................................
56
6.5.1.
SYNTHESIS
STRATEGY
.................................................................................................................
57
6.5.2.
BIOLOGICAL
EVALUATION
.............................................................................................................
59
6.5.3.
CONCLUSION
............................................................................................................................
61
6.6.
CONCLUSION
AND
STRUCTURE
ACTIVITY
RELATIONSHIPS
..........................................................................
61
7.
DESIGN,
SYNTHESIS
AND
EVALUATION
OF
PAR2
ANTAGONISTS
............................................................
63
7.1.
STRUCTURE
BASED
APPROACH
FOR
DRUG
DESIGN
..................................................................................
63
7.2.
DESIGN
OF
LIGANDS
BASED
ON
THE
PAR2
CRYSTAL
STRUCTURE
...............................................................
63
7.2.1.
SYNTHESIS
OF
AZ8838
DERIVATIVES
...........................................................................................
65
7.2.2.
BIOLOGICAL
EVALUATION
.............................................................................................................
67
7.2.3.
CONCLUSION
............................................................................................................................
71
7.3.
DESIGN
OF
LIGANDS
USING
A
PAR2
HOMOLOGY
MODEL
........................................................................
71
7.3.1.
SYNTHESIS
OF
TRICYCLIC
LIGANDS
.................................................................................................
73
7.3.2.
BIOLOGICAL
EVALUATION
.............................................................................................................
75
7.3.3.
CONCLUSION
............................................................................................................................
76
8.
BRET
SENSORS
TO
STUDY
PAR2............................................................................................................
77
8.1.
BIOLUMINESCENCE
RESONANCE
ENERGY
TRANSFER
..............................................................................
77
8.2.
MONITORING
RECEPTOR
TRAFFICKING
USING
BRET
SENSORS
...................................................................
78
8.3.
INHIBITION
OF
RECEPTOR
ENDOCYTOSIS
.............................................................................................
81
8.3.1.
GENERAL
STRATEGIES
TO
INHIBIT
RECEPTOR
ENDOCYTOSIS
............................................................
81
8.3.2.
DESIGN
AND
BIOLOGICAL
EVALUATION
OF
PAR2
TAT-PEPTIDES
....................................................
82
8.4.
NANOBRET
EXPERIMENTS
..............................................................................................................
86
8.4.1.
SYNTHESIS
AND
BIOLOGICAL
EVALUATION
OF
MOLECULAR
PROBES
....................................................
86
8.4.2.
APPROACHES
TOWARDS
NANOBRET
FOR
PAR2...........................................................................
88
8.4.3.
CONCLUSION
............................................................................................................................
93
9.
SUMMARY
.............................................................................................................................................
94
10.
ZUSAMMENFASSUNG
..........................................................................................................................
100
TABLE
OF
CONTENTS
11.
MATERIAL
AND
METHODS
..................................................................................................................
106
11.1.
CHEMISTRY
................................................................................................................................
106
11.1.1.
GENERAL
PROCEDURES
............................................................................................................
106
11.1.2.
EXPERIMENTAL
PROCEDURES
AND
COMPOUND
CHARACTERIZATION
..............................................
113
11.2.
BIOLOGY
....................................................................................................................................
296
11.2.1.
MATERIALS
.............................................................................................................................
296
11.2.2.
METHODS
.............................................................................................................................
312
12.
APPENDIX
..........................................................................................................................................
323
12.1.
ABBREVIATIONS
.........................................................................................................................
323
12.2.
LIST
OF
FIGURES
..........................................................................................................................
327
12.3.
LIST
OF
SCHEMES
.......................................................................................................................
330
12.4.
LIST
OF
TABLES
...........................................................................................................................
331
13.
REFERENCES
......................................................................................................................................
332
14.
CURRICULUM
VITAE
............................................................................................................................
356
|
| any_adam_object | 1 |
| author | Klösel, Ilona 1990- |
| author_GND | (DE-588)119817160X |
| author_facet | Klösel, Ilona 1990- |
| author_role | aut |
| author_sort | Klösel, Ilona 1990- |
| author_variant | i k ik |
| building | Verbundindex |
| bvnumber | BV046227807 |
| ctrlnum | (OCoLC)1126552535 (DE-599)DNB1197761950 |
| discipline | Chemie / Pharmazie Biologie |
| format | Thesis Book |
| fullrecord | <?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01905nam a2200433 c 4500</leader><controlfield tag="001">BV046227807</controlfield><controlfield tag="003">DE-604</controlfield><controlfield tag="005">20200427 </controlfield><controlfield tag="007">t</controlfield><controlfield tag="008">191104s2019 gw a||| m||| 00||| eng d</controlfield><datafield tag="016" ind1="7" ind2=" "><subfield code="a">1197761950</subfield><subfield code="2">DE-101</subfield></datafield><datafield tag="020" ind1=" " ind2=" "><subfield code="c">Broschur</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(OCoLC)1126552535</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)DNB1197761950</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-604</subfield><subfield code="b">ger</subfield><subfield code="e">rda</subfield></datafield><datafield tag="041" ind1="0" ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="044" ind1=" " ind2=" "><subfield code="a">gw</subfield><subfield code="c">XA-DE</subfield></datafield><datafield tag="049" ind1=" " ind2=" "><subfield code="a">DE-29</subfield><subfield code="a">DE-29T</subfield><subfield code="a">DE-355</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">540</subfield><subfield code="2">sdnb</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">570</subfield><subfield code="2">sdnb</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Klösel, Ilona</subfield><subfield code="d">1990-</subfield><subfield code="e">Verfasser</subfield><subfield code="0">(DE-588)119817160X</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Novel ligands for protease-activated receptor 2</subfield><subfield code="b">synthesis and biological investigation = Neuartige Liganden für den Protease-aktivierten Rezeptor 2</subfield><subfield code="c">vorgelegt von Ilona Klösel</subfield></datafield><datafield tag="246" ind1="1" ind2="3"><subfield code="a">Neuartige Liganden für den Protease-aktivierten Rezeptor 2</subfield></datafield><datafield tag="246" ind1="1" ind2="1"><subfield code="a">Neuartige Liganden für den Protease-aktivierten Rezeptor 2</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="a">Erlangen ; Nürnberg</subfield><subfield code="c">[2019]</subfield></datafield><datafield tag="300" ind1=" " ind2=" "><subfield code="a">356 Seiten</subfield><subfield code="b">Illustrationen, Diagramme</subfield><subfield code="c">21 cm</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="b">n</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="b">nc</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="502" ind1=" " ind2=" "><subfield code="b">Dissertation</subfield><subfield code="c">Friedrich-Alexander-Universität Erlangen-Nürnberg</subfield><subfield code="d">2019</subfield></datafield><datafield tag="650" ind1="0" ind2="7"><subfield code="a">Ligand</subfield><subfield code="0">(DE-588)4035711-9</subfield><subfield code="2">gnd</subfield><subfield code="9">rswk-swf</subfield></datafield><datafield tag="650" ind1="0" ind2="7"><subfield code="a">G-Protein gekoppelter Rezeptor</subfield><subfield code="0">(DE-588)7723480-7</subfield><subfield code="2">gnd</subfield><subfield code="9">rswk-swf</subfield></datafield><datafield tag="655" ind1=" " ind2="7"><subfield code="0">(DE-588)4113937-9</subfield><subfield code="a">Hochschulschrift</subfield><subfield code="2">gnd-content</subfield></datafield><datafield tag="689" ind1="0" ind2="0"><subfield code="a">G-Protein gekoppelter Rezeptor</subfield><subfield code="0">(DE-588)7723480-7</subfield><subfield code="D">s</subfield></datafield><datafield tag="689" ind1="0" ind2="1"><subfield code="a">Ligand</subfield><subfield code="0">(DE-588)4035711-9</subfield><subfield code="D">s</subfield></datafield><datafield tag="689" ind1="0" ind2=" "><subfield code="5">DE-604</subfield></datafield><datafield tag="856" ind1="4" ind2="2"><subfield code="m">B:DE-101</subfield><subfield code="q">application/pdf</subfield><subfield code="u">https://d-nb.info/1197761950/04</subfield><subfield code="3">Inhaltsverzeichnis</subfield></datafield><datafield tag="856" ind1="4" ind2="2"><subfield code="m">DNB Datenaustausch</subfield><subfield code="q">application/pdf</subfield><subfield code="u">http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=031606338&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA</subfield><subfield code="3">Inhaltsverzeichnis</subfield></datafield><datafield tag="999" ind1=" " ind2=" "><subfield code="a">oai:aleph.bib-bvb.de:BVB01-031606338</subfield></datafield></record></collection> |
| genre | (DE-588)4113937-9 Hochschulschrift gnd-content |
| genre_facet | Hochschulschrift |
| id | DE-604.BV046227807 |
| illustrated | Illustrated |
| indexdate | 2024-07-10T08:38:53Z |
| institution | BVB |
| language | English |
| oai_aleph_id | oai:aleph.bib-bvb.de:BVB01-031606338 |
| oclc_num | 1126552535 |
| open_access_boolean | |
| owner | DE-29 DE-29T DE-355 DE-BY-UBR |
| owner_facet | DE-29 DE-29T DE-355 DE-BY-UBR |
| physical | 356 Seiten Illustrationen, Diagramme 21 cm |
| publishDate | 2019 |
| publishDateSearch | 2019 |
| publishDateSort | 2019 |
| record_format | marc |
| spelling | Klösel, Ilona 1990- Verfasser (DE-588)119817160X aut Novel ligands for protease-activated receptor 2 synthesis and biological investigation = Neuartige Liganden für den Protease-aktivierten Rezeptor 2 vorgelegt von Ilona Klösel Neuartige Liganden für den Protease-aktivierten Rezeptor 2 Erlangen ; Nürnberg [2019] 356 Seiten Illustrationen, Diagramme 21 cm txt rdacontent n rdamedia nc rdacarrier Dissertation Friedrich-Alexander-Universität Erlangen-Nürnberg 2019 Ligand (DE-588)4035711-9 gnd rswk-swf G-Protein gekoppelter Rezeptor (DE-588)7723480-7 gnd rswk-swf (DE-588)4113937-9 Hochschulschrift gnd-content G-Protein gekoppelter Rezeptor (DE-588)7723480-7 s Ligand (DE-588)4035711-9 s DE-604 B:DE-101 application/pdf https://d-nb.info/1197761950/04 Inhaltsverzeichnis DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=031606338&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Klösel, Ilona 1990- Novel ligands for protease-activated receptor 2 synthesis and biological investigation = Neuartige Liganden für den Protease-aktivierten Rezeptor 2 Ligand (DE-588)4035711-9 gnd G-Protein gekoppelter Rezeptor (DE-588)7723480-7 gnd |
| subject_GND | (DE-588)4035711-9 (DE-588)7723480-7 (DE-588)4113937-9 |
| title | Novel ligands for protease-activated receptor 2 synthesis and biological investigation = Neuartige Liganden für den Protease-aktivierten Rezeptor 2 |
| title_alt | Neuartige Liganden für den Protease-aktivierten Rezeptor 2 |
| title_auth | Novel ligands for protease-activated receptor 2 synthesis and biological investigation = Neuartige Liganden für den Protease-aktivierten Rezeptor 2 |
| title_exact_search | Novel ligands for protease-activated receptor 2 synthesis and biological investigation = Neuartige Liganden für den Protease-aktivierten Rezeptor 2 |
| title_full | Novel ligands for protease-activated receptor 2 synthesis and biological investigation = Neuartige Liganden für den Protease-aktivierten Rezeptor 2 vorgelegt von Ilona Klösel |
| title_fullStr | Novel ligands for protease-activated receptor 2 synthesis and biological investigation = Neuartige Liganden für den Protease-aktivierten Rezeptor 2 vorgelegt von Ilona Klösel |
| title_full_unstemmed | Novel ligands for protease-activated receptor 2 synthesis and biological investigation = Neuartige Liganden für den Protease-aktivierten Rezeptor 2 vorgelegt von Ilona Klösel |
| title_short | Novel ligands for protease-activated receptor 2 |
| title_sort | novel ligands for protease activated receptor 2 synthesis and biological investigation neuartige liganden fur den protease aktivierten rezeptor 2 |
| title_sub | synthesis and biological investigation = Neuartige Liganden für den Protease-aktivierten Rezeptor 2 |
| topic | Ligand (DE-588)4035711-9 gnd G-Protein gekoppelter Rezeptor (DE-588)7723480-7 gnd |
| topic_facet | Ligand G-Protein gekoppelter Rezeptor Hochschulschrift |
| url | https://d-nb.info/1197761950/04 http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=031606338&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
| work_keys_str_mv | AT kloselilona novelligandsforproteaseactivatedreceptor2synthesisandbiologicalinvestigationneuartigeligandenfurdenproteaseaktiviertenrezeptor2 AT kloselilona neuartigeligandenfurdenproteaseaktiviertenrezeptor2 |
There is no print copy available.
Indexes