Influence of Size and Topology on the Efficiency of Sequence-defined Polycationic Carriers for Gene Delivery:
Gespeichert in:
| 1. Verfasser: | |
|---|---|
| Format: | Abschlussarbeit Buch |
| Sprache: | English |
| Veröffentlicht: |
2014
|
| Schlagworte: | |
| Online-Zugang: | kostenfrei kostenfrei Inhaltsverzeichnis |
| Beschreibung: | 120 Blatt graph. Darst. |
| Format: | Langzeitarchivierung gewährleistet, LZA |
Internformat
MARC
| LEADER | 00000nam a2200000zc 4500 | ||
|---|---|---|---|
| 001 | BV041929540 | ||
| 003 | DE-604 | ||
| 005 | 20140725 | ||
| 007 | t | ||
| 008 | 140624s2014 gw d||| m||| 00||| eng d | ||
| 016 | 7 | |a 1050647998 |2 DE-101 | |
| 035 | |a (OCoLC)881620531 | ||
| 035 | |a (DE-599)DNB1050647998 | ||
| 040 | |a DE-604 |b ger |e rakddb | ||
| 041 | 0 | |a eng | |
| 044 | |a gw |c XA-DE-BY | ||
| 049 | |a DE-12 |a DE-19 |a DE-384 |a DE-473 |a DE-703 |a DE-1051 |a DE-824 |a DE-29 |a DE-91 |a DE-1049 |a DE-92 |a DE-739 |a DE-898 |a DE-355 |a DE-706 |a DE-20 |a DE-1102 | ||
| 082 | 0 | |a 610 | |
| 084 | |a 610 |2 sdnb | ||
| 100 | 1 | |a Scholz, Claudia Veronica |d 1985- |e Verfasser |0 (DE-588)105431392X |4 aut | |
| 245 | 1 | 0 | |a Influence of Size and Topology on the Efficiency of Sequence-defined Polycationic Carriers for Gene Delivery |c Claudia Veronica Scholz |
| 264 | 1 | |c 2014 | |
| 300 | |a 120 Blatt |b graph. Darst. | ||
| 336 | |b txt |2 rdacontent | ||
| 337 | |b n |2 rdamedia | ||
| 338 | |b nc |2 rdacarrier | ||
| 502 | |a München, Ludwig-Maximilians-Universität, Diss., 2014 | ||
| 538 | |a Langzeitarchivierung gewährleistet, LZA | ||
| 655 | 7 | |0 (DE-588)4113937-9 |a Hochschulschrift |2 gnd-content | |
| 776 | 0 | 8 | |i Erscheint auch als |n Online-Ausgabe |o urn:nbn:de:bvb:19-168528 |
| 856 | 4 | 1 | |u https://nbn-resolving.org/urn:nbn:de:bvb:19-168528 |x Resolving-System |z kostenfrei |3 Volltext |
| 856 | 4 | 1 | |u http://edoc.ub.uni-muenchen.de/16852/ |x Verlag |z kostenfrei |3 Volltext |
| 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=027372882&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |3 Inhaltsverzeichnis |
| 912 | |a ebook | ||
| 999 | |a oai:aleph.bib-bvb.de:BVB01-027372882 | ||
Datensatz im Suchindex
| _version_ | 1804152303236677632 |
|---|---|
| adam_text | DISSERTATION ZUR ERLANGUNG DES DOKTORGRADES
DER FAKULTAT FUR CHEMIE UND PHARMAZIE
DER LUDWIG-MAXIMILIANS-UNIVERSITAT MUNCHEN
INFLUENCE OF SIZE AND TOPOLOGY ON THE EFFICIENCY
OF SEQUENCE-DEFINED POLYCATIONIC CARRIERS
FOR GENE DELIVERY
CLAUDIA VERONICA SCHOLZ
AUS
RUSSELSHEIM, DEUTSCHLAND
2014
HTTP://D-NB.INFO/1051766273
TABLE OF CONTENTS 4
1 TABLE OF CONTENTS
1 TABLE OF CONTENTS 4
2 INTRODUCTION 8
2.1 NUCLEIC ACID-BASED THERAPIES 8
2.2 SYNTHETIC CARRIER SYSTEMS FOR THE DELIVERY OF NUCLEIC ACIDS 9
2.2.1 FEATURES OF DIFFERENT THERAPEUTIC CARRIER TYPES 9
2.2.2 POLYDISPERSE VERSUS PRECISE CARRIER STRUCTURES 11
2.3 SOLID-PHASE ASSISTED SYNTHESIS: AN APPROACH TO DESIGN
SEQUENCE-DEFINED CARRIERS. 14
2.4 IMPACT OF SIZE ON GENE CARRIER PROPERTIES 15
2.5 INFLUENCE OF TOPOLOGY ON GENE CARRIER PROPERTIES 17
2.6 AIM OF THE THESIS 18
3 MATERIALS AND METHODS 20
3.1 CHEMICALS AND REAGENTS 20
3.2 SOLID-PHASE ASSISTED PEPTIDE SYNTHESIS - GENERAL PROCEDURES 21
3.2.1 AUTOMATED PEPTIDE SYNTHESIS 21
3.2.2 RESIN LOADING 21
3.2.3 DETERMINATION OF THE RESIN LOADING - FMOC QUANTIFICATION 22
3.2.4 KAISER TEST 22
3.2.5 SYNTHESIS OF DIAMINOETHANE MOTIF-CONTAINING BUILDING BLOCKS 23
3.3 SYNTHESIS OF LINEAR (ETHANAMINO)AMIDE OLIGOMERS 26
3.3.1 OLIGOMER ASSEMBLY WITH SUCCESSIVE COUPLINGS 26
3.3.2 OLIGOMER ASSEMBLY VIA CONVERGENT COUPLING STRATEGY 27
3.4 SYNTHESIS OF COMB STRUCTURE OLIGOMERS 28
3.4.1 COMB STRUCTURES SYNTHESIS WITH CONVERGENT COUPLING STRATEGY 28
3.4.2 COMB STRUCTURES VIA BACKBONE ASSEMBLY AND SUBSEQUENT COMB
ATTACHMENT...
30
TABLE OF CONTENTS 5
3.4.3 SYNTHESIS OF A TARGETED COMB STRUCTURE BY THE USE OF THE ODE-ALLOC
ORTHOGONALITY 30
3.4.4 SYNTHESIS OF LINEAR CONTROL SEQUENCES 31
3.5 OLIGOMER PURIFICATION AND ANALYTICAL CHARACTERIZATION 31
3.5.1 SIZE EXCLUSION CHROMATOGRAPHY 31
3.5.2
1
H-NMR SPECTROSCOPY 32
3.5.3 MASS SPECTROMETRY 32
3.5.4 ANALYTICAL REVERSED PHASE HPLC 32
3.5.5 BUFFER CAPACITY - PH TITRATIONS 32
3.5.6 CAPILLARY ELECTROPHORESIS 33
3.5.7 TAYLOR DISPERSION ANALYSIS 33
3.6 BIOPHYSICAL ANALYSES 35
3.6.1 POLYPLEX FORMATION 35
3.6.2 AGAROSE GEL SHIFT ASSAY - PDNA BINDING 35
3.6.3 ETHIDIUM BROMIDE ASSAY - PDNA CONDENSATION 35
3.6.4 DYNAMIC LIGHT SCATTERING - PARTICLE SIZE AND ZETA POTENTIAL 35
3.7 BIOLOGICAL EVALUATION 36
3.7.1 CELL CULTURE 36
3.7.2 FLOW CYTOMETRY - CELLULAR ASSOCIATION AND INTERNALIZATION 36
3.7.3 LUCIFERASE ASSAY
- GENE TRANSFER 36
3.7.4 MTT ASSAY - METABOLIC ACTIVITY 37
3.7.5 CELLTITER-GLO* ASSAY - METABOLIC ACTIVITY 37
3.8 STATISTICS 37
4 RESULTS 38
4.1 EVALUATION OF LINEAR OLIGO(ETHANAMINO)AMIDE CARRIERS OF INCREASING
MOLECULAR WEIGHT
FOR PDNA DELIVERY AND COMPARISON TO LINEAR PEI 40
4.1.1 CARRIER DESIGN AND SYNTHESIS 40
TABLE OF CONTENTS
6
4.1.2 BIOPHYSICAL CHARACTERIZATION: DNA CONDENSATION, PARTICLE SIZE AND
BUFFER
CAPACITY 43
4.1.3 BIOLOGICAL EVALUATION: CELLULAR INTERNALIZATION, GENE TRANSFER AND
CYTOTOXICITY. 46
4.2 ANALYTICAL CHARACTERIZATION OF OLIGO(ETHANAMINO)AMIDES BY CAPILLARY
ELECTROPHORESIS
AND TAYLOR DISPERSION ANALYSIS 50
4.2.1 DETERMINATION OF THE EFFECTIVE MOBILITY OF OLIGO(ETHANAMINO)AMIDES
OF
DIFFERENT LENGTH BY CAPILLARY ELECTROPHORESIS 50
4.2.2 DETERMINATION OF THE HYDRODYNAMIC RADIUS R
H
OF OLIGO(ETHANAMINO)AMIDES OF
DIFFERENT LENGTH BY TAYLOR DISPERSION ANALYSIS 53
4.3 OPTIMIZATION OF COMB-LIKE OLIGOMERS FOR PDNA DELIVERY 56
4.3.1 DESIGN AND SYNTHETIC STRATEGY 56
4.3.2 INCORPORATION OF DIFFERENT FUNCTIONALITIES (CYS, HIS, TRP, ALA,
|3-ALA) 59
4.3.3 APPLICATION OF BUILDING BLOCKS WITH DIFFERENT NUMBER OF
ETHYLENAMINE REPEATING
UNITS 61
4.3.4 INTRODUCTION OF A FUNCTIONALIZATION SITE USING THE DDE-ALLOC
ORTHOGONALITY 67
4.4 COMPARISON OF COMB AND LINEAR TOPOLOGY OF OLIGOMERS FOR PDNA
DELIVERY 71
4.4.1 BIOPHYSICAL CHARACTERIZATION: DNA CONDENSATION, PARTICLE SIZE AND
BUFFER
CAPACITY 71
4.4.2 BIOLOGICAL EVALUATION: CELLULAR ASSOCIATION, INTRACELLULAR UPTAKE,
GENE TRANSFER
AND CYTOTOXICTY 74
5 DISCUSSION 78
5.1 EVALUATION OF LINEAR OLIGO(ETHANAMINO)AMIDE CARRIERS OF INCREASING
MOLECULAR WEIGHT
FOR PDNA DELIVERY AND COMPARISON TO LINEAR PEI 78
5.2 CHARACTERIZATION OF OLIGO(ETHANAMINO)AMIDES BY CAPILLARY
ELECTROPHORESIS AND
TAYLOR DISPERSION ANALYSIS 80
5.3 OPTIMIZATION OF COMB-LIKE OLIGOMERS FOR PDNA DELIVERY 83
5.4 COMPARISON OF COMB AND LINEAR TOPOLOGY OF OLIGOMERS FOR PDNA
DELIVERY 85
6 SUMMARY 88
TABLE OF CONTENTS 7
7 REFERENCES 90
8 APPENDIX 100
8.1 ABBREVIATONS 100
8.2 LIST OF ALL OLIGOMERS 102
8.2.1 LONG LINEAR OLIGO(ETHANAMINO)AMIDE CARRIERS 102
8.2.2 COMB STRUCTURE OLIGOMERS 103
8.2.3 LINEAR CONTROL SEQUENCES 104
8.3 ANALYTICAL DATA 104
8.3.1 N M R SPECTRA 104
8.3.2 ADDITIONAL HPLC CHROMATOGRAMS OF LONG LINEAR STP AND SPH
OLIGO(ETHANAMINO)AMIDES, COMB STRUCTURE OLIGOMERS AND LINEAR CONTROL
SEQUENCES... 115
8.4 PUBLICATIONS 119
8.4.1 ORIGINAL PAPERS 119
8.4.2 REVIEW 119
8.4.3 POSTER PRESENTATIONS 119
9 ACKNOWLEDGEMENTS 120
|
| any_adam_object | 1 |
| author | Scholz, Claudia Veronica 1985- |
| author_GND | (DE-588)105431392X |
| author_facet | Scholz, Claudia Veronica 1985- |
| author_role | aut |
| author_sort | Scholz, Claudia Veronica 1985- |
| author_variant | c v s cv cvs |
| building | Verbundindex |
| bvnumber | BV041929540 |
| collection | ebook |
| ctrlnum | (OCoLC)881620531 (DE-599)DNB1050647998 |
| dewey-full | 610 |
| dewey-hundreds | 600 - Technology (Applied sciences) |
| dewey-ones | 610 - Medicine and health |
| dewey-raw | 610 |
| dewey-search | 610 |
| dewey-sort | 3610 |
| dewey-tens | 610 - Medicine and health |
| discipline | Medizin |
| format | Thesis Book |
| fullrecord | <?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01718nam a2200385zc 4500</leader><controlfield tag="001">BV041929540</controlfield><controlfield tag="003">DE-604</controlfield><controlfield tag="005">20140725 </controlfield><controlfield tag="007">t</controlfield><controlfield tag="008">140624s2014 gw d||| m||| 00||| eng d</controlfield><datafield tag="016" ind1="7" ind2=" "><subfield code="a">1050647998</subfield><subfield code="2">DE-101</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(OCoLC)881620531</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)DNB1050647998</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-604</subfield><subfield code="b">ger</subfield><subfield code="e">rakddb</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-BY</subfield></datafield><datafield tag="049" ind1=" " ind2=" "><subfield code="a">DE-12</subfield><subfield code="a">DE-19</subfield><subfield code="a">DE-384</subfield><subfield code="a">DE-473</subfield><subfield code="a">DE-703</subfield><subfield code="a">DE-1051</subfield><subfield code="a">DE-824</subfield><subfield code="a">DE-29</subfield><subfield code="a">DE-91</subfield><subfield code="a">DE-1049</subfield><subfield code="a">DE-92</subfield><subfield code="a">DE-739</subfield><subfield code="a">DE-898</subfield><subfield code="a">DE-355</subfield><subfield code="a">DE-706</subfield><subfield code="a">DE-20</subfield><subfield code="a">DE-1102</subfield></datafield><datafield tag="082" ind1="0" ind2=" "><subfield code="a">610</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">610</subfield><subfield code="2">sdnb</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Scholz, Claudia Veronica</subfield><subfield code="d">1985-</subfield><subfield code="e">Verfasser</subfield><subfield code="0">(DE-588)105431392X</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Influence of Size and Topology on the Efficiency of Sequence-defined Polycationic Carriers for Gene Delivery</subfield><subfield code="c">Claudia Veronica Scholz</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2014</subfield></datafield><datafield tag="300" ind1=" " ind2=" "><subfield code="a">120 Blatt</subfield><subfield code="b">graph. Darst.</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="a">München, Ludwig-Maximilians-Universität, Diss., 2014</subfield></datafield><datafield tag="538" ind1=" " ind2=" "><subfield code="a">Langzeitarchivierung gewährleistet, LZA</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="776" ind1="0" ind2="8"><subfield code="i">Erscheint auch als</subfield><subfield code="n">Online-Ausgabe</subfield><subfield code="o">urn:nbn:de:bvb:19-168528</subfield></datafield><datafield tag="856" ind1="4" ind2="1"><subfield code="u">https://nbn-resolving.org/urn:nbn:de:bvb:19-168528</subfield><subfield code="x">Resolving-System</subfield><subfield code="z">kostenfrei</subfield><subfield code="3">Volltext</subfield></datafield><datafield tag="856" ind1="4" ind2="1"><subfield code="u">http://edoc.ub.uni-muenchen.de/16852/</subfield><subfield code="x">Verlag</subfield><subfield code="z">kostenfrei</subfield><subfield code="3">Volltext</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=027372882&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA</subfield><subfield code="3">Inhaltsverzeichnis</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">ebook</subfield></datafield><datafield tag="999" ind1=" " ind2=" "><subfield code="a">oai:aleph.bib-bvb.de:BVB01-027372882</subfield></datafield></record></collection> |
| genre | (DE-588)4113937-9 Hochschulschrift gnd-content |
| genre_facet | Hochschulschrift |
| id | DE-604.BV041929540 |
| illustrated | Illustrated |
| indexdate | 2024-07-10T01:08:34Z |
| institution | BVB |
| language | English |
| oai_aleph_id | oai:aleph.bib-bvb.de:BVB01-027372882 |
| oclc_num | 881620531 |
| open_access_boolean | 1 |
| owner | DE-12 DE-19 DE-BY-UBM DE-384 DE-473 DE-BY-UBG DE-703 DE-1051 DE-824 DE-29 DE-91 DE-BY-TUM DE-1049 DE-92 DE-739 DE-898 DE-BY-UBR DE-355 DE-BY-UBR DE-706 DE-20 DE-1102 |
| owner_facet | DE-12 DE-19 DE-BY-UBM DE-384 DE-473 DE-BY-UBG DE-703 DE-1051 DE-824 DE-29 DE-91 DE-BY-TUM DE-1049 DE-92 DE-739 DE-898 DE-BY-UBR DE-355 DE-BY-UBR DE-706 DE-20 DE-1102 |
| physical | 120 Blatt graph. Darst. |
| psigel | ebook |
| publishDate | 2014 |
| publishDateSearch | 2014 |
| publishDateSort | 2014 |
| record_format | marc |
| spelling | Scholz, Claudia Veronica 1985- Verfasser (DE-588)105431392X aut Influence of Size and Topology on the Efficiency of Sequence-defined Polycationic Carriers for Gene Delivery Claudia Veronica Scholz 2014 120 Blatt graph. Darst. txt rdacontent n rdamedia nc rdacarrier München, Ludwig-Maximilians-Universität, Diss., 2014 Langzeitarchivierung gewährleistet, LZA (DE-588)4113937-9 Hochschulschrift gnd-content Erscheint auch als Online-Ausgabe urn:nbn:de:bvb:19-168528 https://nbn-resolving.org/urn:nbn:de:bvb:19-168528 Resolving-System kostenfrei Volltext http://edoc.ub.uni-muenchen.de/16852/ Verlag kostenfrei Volltext DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=027372882&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Scholz, Claudia Veronica 1985- Influence of Size and Topology on the Efficiency of Sequence-defined Polycationic Carriers for Gene Delivery |
| subject_GND | (DE-588)4113937-9 |
| title | Influence of Size and Topology on the Efficiency of Sequence-defined Polycationic Carriers for Gene Delivery |
| title_auth | Influence of Size and Topology on the Efficiency of Sequence-defined Polycationic Carriers for Gene Delivery |
| title_exact_search | Influence of Size and Topology on the Efficiency of Sequence-defined Polycationic Carriers for Gene Delivery |
| title_full | Influence of Size and Topology on the Efficiency of Sequence-defined Polycationic Carriers for Gene Delivery Claudia Veronica Scholz |
| title_fullStr | Influence of Size and Topology on the Efficiency of Sequence-defined Polycationic Carriers for Gene Delivery Claudia Veronica Scholz |
| title_full_unstemmed | Influence of Size and Topology on the Efficiency of Sequence-defined Polycationic Carriers for Gene Delivery Claudia Veronica Scholz |
| title_short | Influence of Size and Topology on the Efficiency of Sequence-defined Polycationic Carriers for Gene Delivery |
| title_sort | influence of size and topology on the efficiency of sequence defined polycationic carriers for gene delivery |
| topic_facet | Hochschulschrift |
| url | https://nbn-resolving.org/urn:nbn:de:bvb:19-168528 http://edoc.ub.uni-muenchen.de/16852/ http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=027372882&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
| work_keys_str_mv | AT scholzclaudiaveronica influenceofsizeandtopologyontheefficiencyofsequencedefinedpolycationiccarriersforgenedelivery |