Targeting the p53-MDM2 and p53-MDMX interaction as a therapeutic strategy for anticancer treatment:
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| Main Author: | |
|---|---|
| Format: | Thesis Book |
| Language: | English |
| Published: |
2012
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| Subjects: | |
| Online Access: | Volltext https://nbn-resolving.org/urn:nbn:de:bvb:91-diss-20120628-1096710-0-4 Inhaltsverzeichnis |
| Physical Description: | IV, 106 S. Ill., graph. Darst. |
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Record in the Search Index
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| adam_text | IMAGE 1
TABLE OF CONTENTS III
TABLE OF CONTENTS
ACKNOWLEDGEMENTS I
PUBLICATIONS II
1. INTRODUCTION 1
1.1. THE CELL CYCLE AND THE ROLE OF P53 1
1.2. STRUCTURE OF THE P53 PROTEIN 3
1.3. QUATERNARY STRUCTURE OF P53 5
1.4. THE P53 PATHWAY 7
1.5. MDM2 AND MDMX 8
1.6. P53-MDM2 AND P53-MDMX DISRUPTING SMALL DRUG-LIKE MOLECULES 12
2. GOAL OF STUDY 15
3. MATERIALS AND METHODS 16
3.1. MATERIALS 16
3.1.1. E-COLI STRAINS 16
3.1.2. PLASMIDS 16
3.1.3. CELL-GROWTH MEDIA AND STOCKS 16
3.1.4. SOLUTIONS AND BUFFERS 18
3.1.5. PEPTIDES USED FOR FP-ASSAY 24
3.1.6. KITS 24
3.1.7. PROTEIN, NUCLEIC ACIDS MARKERS AND SAMPLE LOADING DYES 24
3.1.8. CHROMATOGRAPHY EQUIPMENT, COLUMNS AND MEDIA 25
3.1.9. FLUORESCENT POLARIZATION EQUIPMENT 26
3.2. LABORATORY METHODS AND PRINCIPLES 26
3.2.1. PREPARATION OF PLASMID DNA 26
3.2.2 TRANSFORMATION OF E. COLI 26
3.2.3 PROTEIN CHEMISTRY METHODS & TECHNIQUES 27
3.2.4 NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY (NMR) 30
3.2.5. FLUORESCENCE POLARISATION ASSAY 30
3.2.6 X-RAY CRYSTALLOGRAPHY 31
4. RESULTS AND DISCUSSION 33
4.1. PROTEIN EXPRESSION AND PURIFICATION 33
HTTP://D-NB.INFO/103514185X
IMAGE 2
TABLE OF CONTENTS IV
4.2. ANCHOR.QUERY 35
4.3. AIDA-ASSAY 36
4.4. FP-ASSAY 38
4.5. NOVEL INHIBITORS FOLLOWING THE 3-POINT PHARMACOPHORE MODEL 38
4.5.1. BINDING AFFINITIES OF THE ALKALOID-LIKE SCAFFOLD 38
4.5.2. BINDING AFFINITY OF COMPOUND 9 1 MEASURED WITH HSQC 46
4.5.3. LIGAND EFFICIENCY 47
4.5.4. CRYSTAL STRUCTURE OF THE MDM2-9I COMPLEX 50
4.6. NOVEL INHIBITORS FOLLOWING THE 4-POINT PHARMACOPHORE MODEL 54
4.6.1. BINDING AFFINITY OF COMPOUNDS KK271 AND YH300 54
4.6.2. CRYSTAL STRUCTURE OF THE MDM2-KK271 COMPLEX 54
4.6.3. MOLECULAR DYNAMICS SIMULATIONS OF THE LEU26 POCKET OF MDM2 60
4.6.4. COMPOUND YH300 63
4.6.5. CRYSTAL STRUCTURE OF THE MDM2-YH300 COMPLEX 63
4.7. FLUORINE 69
4.7.1. BINDING AFFINITIES OF THE FLUORINATED COMPOUNDS MEASURED BY THE
FP- AND AIDA-ASSAYS 70
4.7.2. BINDING AFFINITY OF COMPOUND 7E MEASURED BY HSQC 75
4.7.3. CRYSTAL STRUCTURE OF THE MDM2-7E COMPLEX 75
4.8. P53-MDMX INHIBITORS 85
5. SUMMARY 89
6. ZUSAMMENFASSUNG 91
7. REFERENCES 93
|
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| spelling | Wolf, Siglinde Guillermina Morelia Verfasser aut Targeting the p53-MDM2 and p53-MDMX interaction as a therapeutic strategy for anticancer treatment Siglinde Guillermina Morelia Wolf 2012 IV, 106 S. Ill., graph. Darst. txt rdacontent n rdamedia nc rdacarrier München, Techn. Univ., Diss., 2012 Protein p53 (DE-588)4176550-3 gnd rswk-swf Inhibitor (DE-588)4027007-5 gnd rswk-swf (DE-588)4113937-9 Hochschulschrift gnd-content Protein p53 (DE-588)4176550-3 s Inhibitor (DE-588)4027007-5 s DE-604 Erscheint auch als Online-Ausgabe urn:nbn:de:bvb:91-diss-20120628-1096710-0-4 http://mediatum.ub.tum.de/node?id=1096710 Verlag kostenfrei Volltext https://nbn-resolving.org/urn:nbn:de:bvb:91-diss-20120628-1096710-0-4 Resolving-System DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=025894358&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Wolf, Siglinde Guillermina Morelia Targeting the p53-MDM2 and p53-MDMX interaction as a therapeutic strategy for anticancer treatment Protein p53 (DE-588)4176550-3 gnd Inhibitor (DE-588)4027007-5 gnd |
| subject_GND | (DE-588)4176550-3 (DE-588)4027007-5 (DE-588)4113937-9 |
| title | Targeting the p53-MDM2 and p53-MDMX interaction as a therapeutic strategy for anticancer treatment |
| title_auth | Targeting the p53-MDM2 and p53-MDMX interaction as a therapeutic strategy for anticancer treatment |
| title_exact_search | Targeting the p53-MDM2 and p53-MDMX interaction as a therapeutic strategy for anticancer treatment |
| title_full | Targeting the p53-MDM2 and p53-MDMX interaction as a therapeutic strategy for anticancer treatment Siglinde Guillermina Morelia Wolf |
| title_fullStr | Targeting the p53-MDM2 and p53-MDMX interaction as a therapeutic strategy for anticancer treatment Siglinde Guillermina Morelia Wolf |
| title_full_unstemmed | Targeting the p53-MDM2 and p53-MDMX interaction as a therapeutic strategy for anticancer treatment Siglinde Guillermina Morelia Wolf |
| title_short | Targeting the p53-MDM2 and p53-MDMX interaction as a therapeutic strategy for anticancer treatment |
| title_sort | targeting the p53 mdm2 and p53 mdmx interaction as a therapeutic strategy for anticancer treatment |
| topic | Protein p53 (DE-588)4176550-3 gnd Inhibitor (DE-588)4027007-5 gnd |
| topic_facet | Protein p53 Inhibitor Hochschulschrift |
| url | http://mediatum.ub.tum.de/node?id=1096710 https://nbn-resolving.org/urn:nbn:de:bvb:91-diss-20120628-1096710-0-4 http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=025894358&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
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