Biocompatible and precise branched oligomers for pDNA and siRNA delivery:
Gespeichert in:
| 1. Verfasser: | |
|---|---|
| Format: | Abschlussarbeit Buch |
| Sprache: | English |
| Veröffentlicht: |
2013
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| Schlagworte: | |
| Online-Zugang: | kostenfrei http://d-nb.info/1037076346/34 https://nbn-resolving.org/urn:nbn:de:bvb:19-158383 Inhaltsverzeichnis |
| Beschreibung: | 109 S. Ill., graph. Darst. |
Internformat
MARC
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| 100 | 1 | |a Salcher, Eveline Edith |d 1980- |e Verfasser |0 (DE-588)1037879651 |4 aut | |
| 245 | 1 | 0 | |a Biocompatible and precise branched oligomers for pDNA and siRNA delivery |c Edith Salcher |
| 264 | 1 | |c 2013 | |
| 300 | |a 109 S. |b Ill., graph. Darst. | ||
| 336 | |b txt |2 rdacontent | ||
| 337 | |b n |2 rdamedia | ||
| 338 | |b nc |2 rdacarrier | ||
| 502 | |a München, Univ., Diss., 2013 | ||
| 655 | 7 | |0 (DE-588)4113937-9 |a Hochschulschrift |2 gnd-content | |
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Datensatz im Suchindex
| _version_ | 1804150739456491520 |
|---|---|
| adam_text | TABLE OF CONTENTS
1
TABLE OF CONTENTS
1 INTRODUCTION 5
1.1 THERAPEUTIC APPROACH FOR GENETIC DISORDERS 5
1.2 BOTTLENECKS WITHIN NUCLEIC ACID DELIVERY 7
1.3 OVERCOMING THE BARRIERS: NUCLEIC ACID CARRIER SYSTEMS 8
1.3.1 VIRAL VECTORS 8
1.3.2 NON-VIRAL VECTORS 9
1.4 TOWARDS BETTER DEFINED DELIVERY SYSTEMS 13
1.5 SOLID-PHASE PEPTIDE SYNTHESIS (SPPS) ALLOWS ASSEMBLY OF PRECISE,
SEQUENCE DEFINED NUCLEIC ACID CARRIERS 14
1.6 AIMS OF THE THESIS 16
2 MATERIALS AND METHODS 19
2.1 CHEMICALS AND REAGENTS 19
2.2 GENERAL METHODS FOR SPPS-BASED OLIGOMER SYNTHESIS 20
2.2.1 SYNTHESES OF CATIONIC BUILDING BLOCKS 20
2.2.2 GENERAL METHODS FOR OLIGOMERS SYNTHESIS BY MANUAL SPPS 20
2.2.3 DMF TEST ON AMINE IMPURITIES 20
2.2.4 FMOC QUANTIFICATION 21
2.2.5 KAISER TEST 21
2.2.6 INTRODUCTION OF TRITON X-100 21
2.3 SYNTHESES OF FOUR- AND FIVE-ARM OLIGOMERS 22
2.3.1 SYNTHESIS OF FOUR-ARM CORE 22
2.3.2 SYNTHESIS OF FOUR-ARM STP OLIGOMERS 22
2.3.3 SYNTHESIS OF TERMINALLY MODIFIED FOUR-ARM STP, GTT AND SPH
OLIGOMERS. 23
2.3.4 SYNTHESIS OF FIVE-ARM STP OLIGOMERS 23
2.3.5 SYNTHESIS OF HISTIDINE-CONTAINING FOUR-ARM OLIGOMERS 24
2.3.6 SYNTHESIS OF LINEAR STP OLIGOMERS 24
2.3.7 SYNTHESIS OF BOC-CYS(NPYS)-PENTAFLUOROPHENYL ESTER (BCNP-OPFP)..
25
2.3.8 SYNTHESIS OF ACTIVATED PPI CORE (PPI-CNP) 25
2.3.9 ASSEMBLY OF PPI CONJUGATES 26
2.4 METHODS AND DEVICES FOR COMPOUND PURIFICATION AND CHEMICAL
CHARACTERIZATION 26
2.4.1 DIALYSIS 26
HTTP://D-NB.INFO/1037879813
TABLE OF CONTENTS 2
2.4.2 SIZE EXCLUSION CHROMATOGRAPHY 26
2.4.3 ANALYTICAL ION EXCHANGE CHROMATOGRAPHY (IEX-HPLC) 26
2.4.4 ANALYTICAL REVERSED PHASE HPLC (RP-HPLC) 26
2.4.5
1
H-NMR 27
2.4.6 MASS SPECTROMETRY 27
2.4.7 3-NITRO-2-PYRIDINESULFENYL (NPYS) QUANTIFICATION 27
2.4.8 QUANTIFICATION OF 3-NITRO-PYRIDINE-2-THIONE (NPYTHIONE) 27
2.4.9 ELLMAN S ASSAY [158] 27
2.4.10 TRIS(2-CARBOXYETHYL)PHOSPHINE (TCEP) ASSAY 28
2.5 BIOPHYSICAL AND BIOLOGICAL CHARACTERIZATION 28
2.5.1 ACIDIMETRIC TITRATIONS OF HISTIDINE CONTAINING OLIGOMERS 28
2.5.2 POLYPLEX FORMATION 28
2.5.3 MEASUREMENT OF PARTICLE SIZE AND ZETA POTENTIAL 29
2.5.4 PDNA BINDING ASSAY 29
2.5.5 SIRNA BINDING ASSAY 29
2.5.6 PDNA POLYPLEX DISSOCIATION ASSAY 29
2.5.7 ETHIDIUM BROMIDE EXCLUSION ASSAY 29
2.6 CELL CULTURE 30
2.6.1 LUCIFERASE REPORTER GENE EXPRESSION 30
2.6.2 CELL VIABILITY ASSAY (MTT ASSAY) 30
2.6.3 LUCIFERASE GENE SILENCING 31
3 RESULTS 32
3.1 FOUR- AND FIVE-ARM OLIGO(ETHANAMINO)AMIDES FOR PDNA AND SIRNA
DELIVERY 32
3.1.1 INTRODUCTION 32
3.1.2 GENERAL SYNTHESIS AND LIBRARY DESIGN 34
3.1.3 FOUR-ARM STP OLIGOMERS FOR PDNA DELIVERY 36
3.1.4 EFFECT OF INTRODUCTION OF CYSTEINES 38
3.1.5 EFFECT OF STP REPLACEMENT BY SHORTER BUILDING BLOCK GTT 41
3.1.6 EFFECT OF STP REPLACEMENT BY LONGER BUILDING BLOCK SPH 42
3.1.7 FOUR-ARM CYSTEINE CONTAINING STP, GTT AND SPH OLIGOMERS FOR SIRNA
DELIVERY 44
3.1.8 FIVE-ARM STP OLIGOMERS FOR PDNA AND SIRNA DELIVERY 47
3.2 HISTIDINE-CONTAINING STP AND GTT OLIGOMERS 49
TABLE OF CONTENTS 3
3.2.1 INTRODUCTION 49
3.2.2 LIBRARY DESIGN AND CHEMICAL CHARACTERIZATION 49
3.2.3 BIOPHYSICAL AND BIOLOGICAL CHARACTERIZATION 52
3.3 POLYPROPYLENIMINE (PPI) CONJUGATES FOR PDNA DELIVERY 58
3.3.1 INTRODUCTION 58
3.3.2 SYNTHETIC CONCEPT 59
3.3.3 CHEMICAL CHARACTERIZATION 61
3.3.4 BIOPHYSICAL AND BIOLOGICAL CHARACTERIZATION 62
4 DISCUSSION 65
4.1 FOUR- AND FIVE-ARM OLIGO(ETHANAMINO)AMIDES FOR PDNA AND SIRNA
DELIVERY65
4.2 HISTIDINE-CONTAINING STP AND GTT OLIGOMERS 67
4.3 POLYPROPYLENIMINE (PPI) CONJUGATES FOR PDNA DELIVERY 68
5 CONCLUSION AND OUTLOOK 70
6 SUMMARY 71
7 APPENDIX 73
7.1 LIST OF USED COMPOUNDS 73
7.1.1 FOUR- AND FIVE-ARM OLIGOMERS 73
7.1.2 LINEAR CYSTEINE-CONTAINING STP OLIGOMERS 74
7.1.3 PPI CONJUGATES 74
7.2 ANALYTICAL DATA 75
7.2.1 FOUR- AND FIVE-ARM OLIGOMERS 75
7.2.2 LINEAR CYSTEINE-CONTAINING STP OLIGOMERS 82
7.2.3 PPI CONJUGATES 83
7.3 ADDITIONAL ANALYTICAL ION EXCHANGE CHROMATOGRAPHY TRACES OF FOUR-ARM
UNMODIFIED STP OLIGOMERS 84
7.4 AFM IMAGES 85
7.5 ADDITIONAL PARTICLE SIZE AND ZETA POTENTIAL MEASUREMENTS 86
7.5.1 FIVE-ARM OLIGOMERS AFTER COMPLEXATION WITH PDNA AT N/P 12 86
7.5.2 SIZE AND ZETA POTENTIAL OF SIRNA POLYPLEXES 86
7.6 ABBREVIATIONS 87
7.7 PUBLICATIONS 89
7.7.1 ORIGINAL PAPERS 89
TABLE OF CONTENTS 4
7.7.2 BOOK CHAPTERS 89
7.7.3 POSTER PRESENTATION 90
7.7.4 ORAL PRESENTATION 90
8 REFERENCES 91
9 ACKNOWLEDGEMENTS 107
10 CURRICULUM VITAE 109
|
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| dewey-full | 610 570 |
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| dewey-ones | 610 - Medicine and health 570 - Biology |
| dewey-raw | 610 570 |
| dewey-search | 610 570 |
| dewey-sort | 3610 |
| dewey-tens | 610 - Medicine and health 570 - Biology |
| discipline | Chemie / Pharmazie Biologie Medizin |
| format | Thesis Book |
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| indexdate | 2024-07-10T00:43:43Z |
| institution | BVB |
| language | English |
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| physical | 109 S. Ill., graph. Darst. |
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| spelling | Salcher, Eveline Edith 1980- Verfasser (DE-588)1037879651 aut Biocompatible and precise branched oligomers for pDNA and siRNA delivery Edith Salcher 2013 109 S. Ill., graph. Darst. txt rdacontent n rdamedia nc rdacarrier München, Univ., Diss., 2013 (DE-588)4113937-9 Hochschulschrift gnd-content Erscheint auch als Online-Ausgabe urn:nbn:de:bvb:19-158383 http://edoc.ub.uni-muenchen.de/15838/ Verlag kostenfrei Volltext http://d-nb.info/1037076346/34 Langzeitarchivierung Nationalbibliothek https://nbn-resolving.org/urn:nbn:de:bvb:19-158383 Resolving-System DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=026246183&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Salcher, Eveline Edith 1980- Biocompatible and precise branched oligomers for pDNA and siRNA delivery |
| subject_GND | (DE-588)4113937-9 |
| title | Biocompatible and precise branched oligomers for pDNA and siRNA delivery |
| title_auth | Biocompatible and precise branched oligomers for pDNA and siRNA delivery |
| title_exact_search | Biocompatible and precise branched oligomers for pDNA and siRNA delivery |
| title_full | Biocompatible and precise branched oligomers for pDNA and siRNA delivery Edith Salcher |
| title_fullStr | Biocompatible and precise branched oligomers for pDNA and siRNA delivery Edith Salcher |
| title_full_unstemmed | Biocompatible and precise branched oligomers for pDNA and siRNA delivery Edith Salcher |
| title_short | Biocompatible and precise branched oligomers for pDNA and siRNA delivery |
| title_sort | biocompatible and precise branched oligomers for pdna and sirna delivery |
| topic_facet | Hochschulschrift |
| url | http://edoc.ub.uni-muenchen.de/15838/ http://d-nb.info/1037076346/34 https://nbn-resolving.org/urn:nbn:de:bvb:19-158383 http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=026246183&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
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