Biomimetic screening of class B G protein-coupled receptors: design of tailored ligands for the Corticotropin-Releasing-Hormone receptor
Gespeichert in:
| 1. Verfasser: | |
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| Format: | Abschlussarbeit Buch |
| Sprache: | English |
| Veröffentlicht: |
2012
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| Schlagworte: | |
| Online-Zugang: | kostenfrei http://d-nb.info/1025047044/34 https://nbn-resolving.org/urn:nbn:de:bvb:19-146182 Inhaltsverzeichnis |
| Beschreibung: | 189 S. graph. Darst. |
Internformat
MARC
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| 100 | 1 | |a Devigny, Christian |d 1982- |e Verfasser |0 (DE-588)102514421X |4 aut | |
| 245 | 1 | 0 | |a Biomimetic screening of class B G protein-coupled receptors |b design of tailored ligands for the Corticotropin-Releasing-Hormone receptor |c Christian Serge Marie Devigny |
| 264 | 1 | |c 2012 | |
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| 337 | |b n |2 rdamedia | ||
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| 502 | |a München, Univ., Diss., 2012 | ||
| 655 | 7 | |0 (DE-588)4113937-9 |a Hochschulschrift |2 gnd-content | |
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Datensatz im Suchindex
| _version_ | 1804149499909636096 |
|---|---|
| adam_text | IMAGE 1
CONTENTS
TABLE OF CONTENTS
ABBREVIATIONS 7
ABSTRACT 1 1
ZUSAMMENFASSUNG 13
1 INTRODUCTION 15
1.1 STRESS AND THE HYPOTHALAMIC-PITUITARY-ADRENAL AXIS 15
1.2 IMPLICATION OF THE HPA AXIS IN PSYCHIATRIC DISORDERS 17
1.3 THE CRH RECEPTOR AND ITS LIGANDS 19
1.3.1 THE CRHR: STRUCTURE, LOCALIZATION AND FUNCTION 19
1.3.2 CRH AND CRH-LIKE PEPTIDES 20
1.3.3 PEPTIDE LIGANDS BINDING MECHANISM 22
1.3.4 G PROTEIN-COUPLED RECEPTOR-DEPENDENT SIGNALING CASCADES 24
1.4 CRHR! ANTAGONISTS 26
1.4.1 PEPTIDE ANTAGONISTS 26
1.4.2 CRHRI NON-PEPTIDE LIGANDS 27
2 OBJECTIVE OF THE STUDY 3 1
3 RESULTS AND DISCUSSION 33
3.1 PEPTIDE-PEPTIDE CONJUGATES AS CRH MIMICS 33
3.1.1 CHOICE O F A LIGATION TECHNIQUE FOR THE SYNTHESIS O F BIOMIMETIC
PROBES 33
3.1.2 SYNTHESIS AND CHARACTERIZATION O F CRHRI-ECDL HIGH AFFINITY PROBES
35
3.1.3 SYNTHESIS O F A CLICKED BIOMIMETIC PROBE: PROOF O F CONCEPT 39
3.1.4 UROCORTINL 115 C- AND N-TERMINAL TRUNCATION: CHARACTERIZATION O F
A MINIMAL CRHR! STIMULATION SEQUENCE 42
3.1.5 ALTERNATIVE LIGATION METHOD: THE HYDRAZONE BIOCONJUGATION OF A UCN
4 15 BIOMIMETIC PROBE 45
3.1.6 ROLE O F THE ETHYLENE GLYCOL CONNECTOR BETWEEN THE TWO LIGANDS
BINDING DOMAINS 49
3.2 UROCORTINL 4 15 BIOMIMETIC SCREENING 54
3.2.1 SYNTHESIS AND POTENCY EVALUATION OF A UROCOTINL 415 PEPTIDE
CONJUGATE LIBRARY 54
3.2.2 PURIFICATION O F EXEMPLARY CONJUGATES: VALIDATION O F THE CRUDE
BIOMIMETIC SCREENING ....60
3.2.3 SYNTHESIS AND EVALUATION O F OPTIMIZED UCN 415 PEPTIDE PROBES 63
3.2.4 PHARMACOLOGICAL CHARACTERIZATION O F A CRHR R TMD SPECIFIC PROBE
72
3
HTTP://D-NB.INFO/1025144244
IMAGE 2
CONTENTS
3.2.5 SYNTHESIS AND EVALUATION O F A PEPTIDE AMIDE LIBRARY 8 1
3.2.6 STRUCTURE-ACTIVITY-RELATIONSHIP AT [PHE N ]UCN 415 84
3.2.7 SUMMARY O F THE UCN BIOMIMETIC SCREENING 86
3.3 BIOMIMETIC SCREENING OF A SYNTHETIC CRHRI MODULATOR: ASTRESSIN 88
3.3.1 EVALUATION OF ASTRESSIN CONJUGATES: RATIONALE AND PROOF O F
CONCEPT 89
3.3.2 ASTRESSIN 1 14 TRUNCATIONS: CHARACTERIZATION OF A MINIMAL
INHIBITION SEQUENCE 9 1
3.3.3 ROLE OF THE ASTRESSIN 111 CONJUGATE MIDDLE DOMAIN 93
3.3.4 ASTRESSIN 1 11 STIMULATION BIOMIMETIC SCREENING 96
3.3.5 ASTRESSIN 1 11 INHIBITION BIOMIMETIC SCREENING 100
3.3.6 EVALUATION OF MULTISUBSTITUTED ASTRESSIN 1 11 BIOMIMETIC PROBES
104
3.3.7 SUMMARY O F THE ASTRESSIN BIOMIMETIC SCREENING I L L
3.4 SYNTHESIS AND CHARACTERIZATION O F NONPEPTIDE CRHRI ANTAGONISTS 113
4 CONCLUSION 117
5 MATERIAL AND METHODS 119
5.1 CHEMICAL METHODS 119
5.1.1 NUCLEAR MAGNETIC RESONANCE 119
5.1.2 MASS SPECTROMETRY 119
5.1.3 LIQUID CHROMATOGRAPHY-MASS SPECTROMETRY 119
5.1.4 HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY 119
5.1.5 FLASH CHROMATOGRAPHY 120
5.1.6 THIN LAYER CHROMATOGRAPHY 120
5.1.7 CHEMICALS 121
5.1.8 SOLVENTS 126
5.1.9 OTHERS MATERIALS 127
5.2 SYNTHETIC METHODS 128
5.2.1 SYNTHESIS OF AZIDE-FUNCTIONALIZED SPACERS 128
5.2.2 SYNTHESIS O F HNA AND SFB MODIFICATION REAGENTS 135
5.2.3 SOLID PHASE SYNTHESIS O F PEPTIDES 137
5.2.4 THE BIOCONJUGATION O F PEPTIDE FRAGMENTS 154
5.2.5 SYNTHESIS OF NONPEPTIDE CRHRI ANTAGONISTS 166
5.3 CAMP CELL-BASED ASSAYS 172
5.3.1 STIMULATION ASSAY TYPICAL PROTOCOL 173
5.3.2 ^INHIBITION ASSAY STANDARD PROTOCOL 173
5.4 DATA ANALYSIS 176
4
IMAGE 3
CONTENTS
REFERENCES 177
ACKNOWLEDGMENTS 187
CURRICULUM VITAE 189
5
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| id | DE-604.BV040442839 |
| illustrated | Illustrated |
| indexdate | 2024-07-10T00:24:00Z |
| institution | BVB |
| language | English |
| oai_aleph_id | oai:aleph.bib-bvb.de:BVB01-025290641 |
| oclc_num | 815933380 |
| open_access_boolean | 1 |
| owner | DE-384 DE-473 DE-BY-UBG DE-703 DE-1051 DE-824 DE-29 DE-12 DE-91 DE-BY-TUM DE-19 DE-BY-UBM DE-1049 DE-92 DE-739 DE-898 DE-BY-UBR DE-355 DE-BY-UBR DE-706 DE-20 DE-1102 |
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| physical | 189 S. graph. Darst. |
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| spelling | Devigny, Christian 1982- Verfasser (DE-588)102514421X aut Biomimetic screening of class B G protein-coupled receptors design of tailored ligands for the Corticotropin-Releasing-Hormone receptor Christian Serge Marie Devigny 2012 189 S. graph. Darst. txt rdacontent n rdamedia nc rdacarrier München, Univ., Diss., 2012 (DE-588)4113937-9 Hochschulschrift gnd-content Erscheint auch als Online-Ausgabe urn:nbn:de:bvb:19-146182 http://edoc.ub.uni-muenchen.de/14618/ Verlag kostenfrei Volltext http://d-nb.info/1025047044/34 Langzeitarchivierung Nationalbibliothek https://nbn-resolving.org/urn:nbn:de:bvb:19-146182 Resolving-System DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=025290641&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Devigny, Christian 1982- Biomimetic screening of class B G protein-coupled receptors design of tailored ligands for the Corticotropin-Releasing-Hormone receptor |
| subject_GND | (DE-588)4113937-9 |
| title | Biomimetic screening of class B G protein-coupled receptors design of tailored ligands for the Corticotropin-Releasing-Hormone receptor |
| title_auth | Biomimetic screening of class B G protein-coupled receptors design of tailored ligands for the Corticotropin-Releasing-Hormone receptor |
| title_exact_search | Biomimetic screening of class B G protein-coupled receptors design of tailored ligands for the Corticotropin-Releasing-Hormone receptor |
| title_full | Biomimetic screening of class B G protein-coupled receptors design of tailored ligands for the Corticotropin-Releasing-Hormone receptor Christian Serge Marie Devigny |
| title_fullStr | Biomimetic screening of class B G protein-coupled receptors design of tailored ligands for the Corticotropin-Releasing-Hormone receptor Christian Serge Marie Devigny |
| title_full_unstemmed | Biomimetic screening of class B G protein-coupled receptors design of tailored ligands for the Corticotropin-Releasing-Hormone receptor Christian Serge Marie Devigny |
| title_short | Biomimetic screening of class B G protein-coupled receptors |
| title_sort | biomimetic screening of class b g protein coupled receptors design of tailored ligands for the corticotropin releasing hormone receptor |
| title_sub | design of tailored ligands for the Corticotropin-Releasing-Hormone receptor |
| topic_facet | Hochschulschrift |
| url | http://edoc.ub.uni-muenchen.de/14618/ http://d-nb.info/1025047044/34 https://nbn-resolving.org/urn:nbn:de:bvb:19-146182 http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=025290641&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
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