Totalsynthese von Ampullosporin und Analoga zur Ermittlung von morphogenen und neuroleptischen Struktur-Konformations-Wirkungs-Beziehungen:
Gespeichert in:
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| Format: | Buch |
| Sprache: | German |
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2003
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| Online-Zugang: | Inhaltsverzeichnis |
| Beschreibung: | Jena, Univ., Diss., 2003 |
| Beschreibung: | 98 S. Ill., graph. Darst. : 21 cm |
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| adam_text | TOTALSYNTHESE VON AMPULLOSPORIN UND ANALOGA ZUR ERMITTLUNG VON
MORPHOGENEN UND NEUROLEPTISCHEN
STRUKTUR-KONFORMATIONS-WIRKUNGS-BEZIEHUNGEN DISSERTATION ZUR ERLANGUNG
DES AKADEMISCHEN GRADES DOCTOR RERUM NATURALIUM (DR. RER. NAT.)
VORGELEGT DEM RAT DER BIOLOGISCH-PHARMAZEUTISCHEN FAKUMT DER
FRIEDRICH-SCHILLER-UNIVERSITAT JENA VON DIPLOMINGENIEURIN-BIOTECHNOLOGIN
HOAI-HUONG NGUYEN GEBOREN AM 19.08.1964 IN HANOI, VIETNAM CONTENTS
CONTENTS PAGES 1 INTRODUCTION 1 2 BACKGROUND 2 2.1. PEPTAIBOLS 2 2.1.1.
PRIMARY STRUCTURE AND CLASSIFICATION 2 2.1.2. BIOLOGICAL ACTIVITIES 4
2.1.3. MEMBRANE-MODIFYING ACTIVITIES 5 2.1.4. STRUCTURE-FUNCTION
RELATIONSHIP STUDIES 9 2.1.5. CONFORMATIONAL STUDIES 12 2.2. NEUROLEPTIC
ACTIVITIES 13 2.2.1. DOPAMINE HYPOTHESIS OF SCHIZOPHRENIA 13 2.2.2.
SEROTONIN-DOPAMINE HYPOTHESIS 15 2.2.3. N-METHYL-D-ASPARTATE RECEPTOR
HYPOTHESIS 15 2.2.4. VIRAL HYPOTHESIS 15 2.2.5. HYPOTHERMIA - SIDE
EFFECT AND INDICATOR OF NEUROLEPTIC DRUGS 15 2.3. AMPULLOSPORINS 16
2.3.1. NATIVE AMPULLOSPORINS 16 2.3.2. MEMBRANE MODIFYING ACTIVITY OF
NATIVE AMPULLOSPORINS 16 2.3.3. CRYSTAL STRUCTURE OF AMP A 17 2.3.4.
BIOLOGICAL ACTIVITIES OF NATIVE AMPULLOSPORINS 18 2.3.4.1. PIGMENT
INDUCTION ACTIVITY 18 2.3.4.2. HYPOTHERMIC AND NEUROLEPTIC EFFECTS 19
2.3.4.3. CORRELATION BETWEEN BIOLOGICAL ACTIVITIES OF NATIVE 19
AMPULLOSPORINS AND THEIR MEMBRANE MODIFYING ACTIVITIES 2.4. HISTORY OF
PEPTAIBOL SYNTHESIS 19 3 AIM 23 CONTENTS 4 RESULTS AND DISCUSSIONS 24
4.1. SOLID PHASE SYNTHESIS OF AMPA ANALOGUES 24 4.1.1. OPTIMUM PROCEDURE
FOR SOLID PHASE SYNTHESIS OF AMPA 24 4.1.1.1. COUPLING REAGENTS 24
4.1.1.2. CLEAVAGE METHODS 25 4.1.2. SOLID PHASE SYNTHESIS OF AMPA
ANALOGUES 29 4.2. ENZYMATIC STABILITY OF AMPA ANALOGUES 34 4.3.
BIOLOGICAL ACTIVITIES OF AMPA ANALOGUES 34 4.3.1. PIGMENT INDUCTION 36
4.3.2. HYPOTHERMIC EFFECT AND LOCOMOTOR ACTIVITY IN MICE 38 4.4.
CONFORMATIONAL STUDIES OF AMPA ANALOGUES USING CIRCULAR 42 DICHROISM
4.4.1 CIRCULAR DICHROISM STUDY OF AMPA 42 4.4.1.1. CD SPECTRA OF AMPA IN
WATER AND ORGANIC SOLVENTS 42 A A.I.2. CD SPECTRA OF AMPA IN MEMBRANE
MIMETIC SOLVENTS 46 4.4.1.3. ESTIMATION OF HELICITY 48 4.4.1.4. THERMAL
STABILITY 49 4.4.2. CD STUDY OF AMPA ANALOGUES 50 4.4.2.1. N-TERMINAL
MODIFIED ANALOGUES 50 4.4.2.2. C-TERMINAL MODIFIED ANALOGUES 55 4.4.2.3.
ANALOGUES WITH MODIFIED SIDE CHAINS 55 4.4.2.4. AIB SUBSTITUTED
ANALOGUES 56 4.5. MEMBRANE-MODIFYING ACTIVITY OF AMPA ANALOGUES 58
4.5.1. CURRENT-VOLTAGE (I-V) CURVE OF THE SYNTHETIC AMPA 58 4.5.2
COMPARISON OF CHANNEL ACTIVITY OF AMPA ANALOGUES AND 59 ALAMETHICIN 4.6.
IN VITRO RECEPTOR BINDING PROPERTIES OF AMPA 62 4.7. SPECIFIC
NEUROLEPTIC TESTS OF AMPA ANALOGUES 63 CONTENTS 5
SUMMARY/ZUSAMMENFASSUNG 65/69 6. EXPERIMENTAL PART 73 6.1. MATERIALS 73
6.2. METHODS 74 6.2.1 ANALYTICAL CHARACTERIZATION 74 6.2.2. SOLID PHASE
PEPTIDE SYNTHESIS 75 6.2.2.1. SYNTHESIS OF AMPA AND ANALOGUES WITH A
C-TERMINAL AMINO 75 ALCOHOL 6.2.2.2. SYNTHESIS OF OTHER ANALOGUES 76
6.2.3. ENZYMATIC DEGRADATION 77 6.2.4. BIOLOGICAL ACTIVITY STUDIES 78
6.2.4.1. PIGMENT INDUCTION ON PHOMA DESTRUCTIVA 78 6.2.4.2. HYPOTHERMIA
AND INHIBITION OF LOCOMOTOR ACTIVITY IN MICE 78 6.2.5. CIRCULAR
DICHROISM STUDIES 80 6.2.6. MACROSCOPIC CONDUCTANCE MEASUREMENT 81
6.2.6.1. I-V RELATIONSHIP OF SYNTHETIC AMPA 81 6.2.6.2. COMPARISON OF
MEMBRANE ACTIVITY OF AMPA ANALOGUES AND 82 ALAMETHICIN 6.2.7.
RADIOLIGAND BINDING ASSAY 82 6.2.8. SPECIFIC NEUROLEPTIC TESTS 83 7
REFERENCES 84
|
| adam_txt |
TOTALSYNTHESE VON AMPULLOSPORIN UND ANALOGA ZUR ERMITTLUNG VON
MORPHOGENEN UND NEUROLEPTISCHEN
STRUKTUR-KONFORMATIONS-WIRKUNGS-BEZIEHUNGEN DISSERTATION ZUR ERLANGUNG
DES AKADEMISCHEN GRADES DOCTOR RERUM NATURALIUM (DR. RER. NAT.)
VORGELEGT DEM RAT DER BIOLOGISCH-PHARMAZEUTISCHEN FAKUMT DER
FRIEDRICH-SCHILLER-UNIVERSITAT JENA VON DIPLOMINGENIEURIN-BIOTECHNOLOGIN
HOAI-HUONG NGUYEN GEBOREN AM 19.08.1964 IN HANOI, VIETNAM CONTENTS
CONTENTS PAGES 1 INTRODUCTION 1 2 BACKGROUND 2 2.1. PEPTAIBOLS 2 2.1.1.
PRIMARY STRUCTURE AND CLASSIFICATION 2 2.1.2. BIOLOGICAL ACTIVITIES 4
2.1.3. MEMBRANE-MODIFYING ACTIVITIES 5 2.1.4. STRUCTURE-FUNCTION
RELATIONSHIP STUDIES 9 2.1.5. CONFORMATIONAL STUDIES 12 2.2. NEUROLEPTIC
ACTIVITIES 13 2.2.1. DOPAMINE HYPOTHESIS OF SCHIZOPHRENIA 13 2.2.2.
SEROTONIN-DOPAMINE HYPOTHESIS 15 2.2.3. N-METHYL-D-ASPARTATE RECEPTOR
HYPOTHESIS 15 2.2.4. VIRAL HYPOTHESIS 15 2.2.5. HYPOTHERMIA - SIDE
EFFECT AND INDICATOR OF NEUROLEPTIC DRUGS 15 2.3. AMPULLOSPORINS 16
2.3.1. NATIVE AMPULLOSPORINS 16 2.3.2. MEMBRANE MODIFYING ACTIVITY OF
NATIVE AMPULLOSPORINS 16 2.3.3. CRYSTAL STRUCTURE OF AMP A 17 2.3.4.
BIOLOGICAL ACTIVITIES OF NATIVE AMPULLOSPORINS 18 2.3.4.1. PIGMENT
INDUCTION ACTIVITY 18 2.3.4.2. HYPOTHERMIC AND NEUROLEPTIC EFFECTS 19
2.3.4.3. CORRELATION BETWEEN BIOLOGICAL ACTIVITIES OF NATIVE 19
AMPULLOSPORINS AND THEIR MEMBRANE MODIFYING ACTIVITIES 2.4. HISTORY OF
PEPTAIBOL SYNTHESIS 19 3 AIM 23 CONTENTS 4 RESULTS AND DISCUSSIONS 24
4.1. SOLID PHASE SYNTHESIS OF AMPA ANALOGUES 24 4.1.1. OPTIMUM PROCEDURE
FOR SOLID PHASE SYNTHESIS OF AMPA 24 4.1.1.1. COUPLING REAGENTS 24
4.1.1.2. CLEAVAGE METHODS 25 4.1.2. SOLID PHASE SYNTHESIS OF AMPA
ANALOGUES 29 4.2. ENZYMATIC STABILITY OF AMPA ANALOGUES 34 4.3.
BIOLOGICAL ACTIVITIES OF AMPA ANALOGUES 34 4.3.1. PIGMENT INDUCTION 36
4.3.2. HYPOTHERMIC EFFECT AND LOCOMOTOR ACTIVITY IN MICE 38 4.4.
CONFORMATIONAL STUDIES OF AMPA ANALOGUES USING CIRCULAR 42 DICHROISM
4.4.1 CIRCULAR DICHROISM STUDY OF AMPA 42 4.4.1.1. CD SPECTRA OF AMPA IN
WATER AND ORGANIC SOLVENTS 42 A A.I.2. CD SPECTRA OF AMPA IN MEMBRANE
MIMETIC SOLVENTS 46 4.4.1.3. ESTIMATION OF HELICITY 48 4.4.1.4. THERMAL
STABILITY 49 4.4.2. CD STUDY OF AMPA ANALOGUES 50 4.4.2.1. N-TERMINAL
MODIFIED ANALOGUES 50 4.4.2.2. C-TERMINAL MODIFIED ANALOGUES 55 4.4.2.3.
ANALOGUES WITH MODIFIED SIDE CHAINS 55 4.4.2.4. AIB SUBSTITUTED
ANALOGUES 56 4.5. MEMBRANE-MODIFYING ACTIVITY OF AMPA ANALOGUES 58
4.5.1. CURRENT-VOLTAGE (I-V) CURVE OF THE SYNTHETIC AMPA 58 4.5.2
COMPARISON OF CHANNEL ACTIVITY OF AMPA ANALOGUES AND 59 ALAMETHICIN 4.6.
IN VITRO RECEPTOR BINDING PROPERTIES OF AMPA 62 4.7. SPECIFIC
NEUROLEPTIC TESTS OF AMPA ANALOGUES 63 CONTENTS 5
SUMMARY/ZUSAMMENFASSUNG 65/69 6. EXPERIMENTAL PART 73 6.1. MATERIALS 73
6.2. METHODS 74 6.2.1 ANALYTICAL CHARACTERIZATION 74 6.2.2. SOLID PHASE
PEPTIDE SYNTHESIS 75 6.2.2.1. SYNTHESIS OF AMPA AND ANALOGUES WITH A
C-TERMINAL AMINO 75 ALCOHOL 6.2.2.2. SYNTHESIS OF OTHER ANALOGUES 76
6.2.3. ENZYMATIC DEGRADATION 77 6.2.4. BIOLOGICAL ACTIVITY STUDIES 78
6.2.4.1. PIGMENT INDUCTION ON PHOMA DESTRUCTIVA 78 6.2.4.2. HYPOTHERMIA
AND INHIBITION OF LOCOMOTOR ACTIVITY IN MICE 78 6.2.5. CIRCULAR
DICHROISM STUDIES 80 6.2.6. MACROSCOPIC CONDUCTANCE MEASUREMENT 81
6.2.6.1. I-V RELATIONSHIP OF SYNTHETIC AMPA 81 6.2.6.2. COMPARISON OF
MEMBRANE ACTIVITY OF AMPA ANALOGUES AND 82 ALAMETHICIN 6.2.7.
RADIOLIGAND BINDING ASSAY 82 6.2.8. SPECIFIC NEUROLEPTIC TESTS 83 7
REFERENCES 84 |
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| index_date | 2024-07-02T13:47:56Z |
| indexdate | 2024-07-09T20:34:41Z |
| institution | BVB |
| language | German |
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| spelling | Nguyen, Hoai-Huong 1964- Verfasser (DE-588)124954669 aut Totalsynthese von Ampullosporin und Analoga zur Ermittlung von morphogenen und neuroleptischen Struktur-Konformations-Wirkungs-Beziehungen von Hoai-Huong Nguyen 2003 98 S. Ill., graph. Darst. : 21 cm txt rdacontent n rdamedia nc rdacarrier Jena, Univ., Diss., 2003 Struktur-Aktivitäts-Beziehung (DE-588)4183784-8 gnd rswk-swf Ampullosporin A (DE-588)7516069-9 gnd rswk-swf Totalsynthese (DE-588)4412308-5 gnd rswk-swf (DE-588)4113937-9 Hochschulschrift gnd-content Ampullosporin A (DE-588)7516069-9 s Totalsynthese (DE-588)4412308-5 s Struktur-Aktivitäts-Beziehung (DE-588)4183784-8 s b DE-604 GBV Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=014604836&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Nguyen, Hoai-Huong 1964- Totalsynthese von Ampullosporin und Analoga zur Ermittlung von morphogenen und neuroleptischen Struktur-Konformations-Wirkungs-Beziehungen Struktur-Aktivitäts-Beziehung (DE-588)4183784-8 gnd Ampullosporin A (DE-588)7516069-9 gnd Totalsynthese (DE-588)4412308-5 gnd |
| subject_GND | (DE-588)4183784-8 (DE-588)7516069-9 (DE-588)4412308-5 (DE-588)4113937-9 |
| title | Totalsynthese von Ampullosporin und Analoga zur Ermittlung von morphogenen und neuroleptischen Struktur-Konformations-Wirkungs-Beziehungen |
| title_auth | Totalsynthese von Ampullosporin und Analoga zur Ermittlung von morphogenen und neuroleptischen Struktur-Konformations-Wirkungs-Beziehungen |
| title_exact_search | Totalsynthese von Ampullosporin und Analoga zur Ermittlung von morphogenen und neuroleptischen Struktur-Konformations-Wirkungs-Beziehungen |
| title_exact_search_txtP | Totalsynthese von Ampullosporin und Analoga zur Ermittlung von morphogenen und neuroleptischen Struktur-Konformations-Wirkungs-Beziehungen |
| title_full | Totalsynthese von Ampullosporin und Analoga zur Ermittlung von morphogenen und neuroleptischen Struktur-Konformations-Wirkungs-Beziehungen von Hoai-Huong Nguyen |
| title_fullStr | Totalsynthese von Ampullosporin und Analoga zur Ermittlung von morphogenen und neuroleptischen Struktur-Konformations-Wirkungs-Beziehungen von Hoai-Huong Nguyen |
| title_full_unstemmed | Totalsynthese von Ampullosporin und Analoga zur Ermittlung von morphogenen und neuroleptischen Struktur-Konformations-Wirkungs-Beziehungen von Hoai-Huong Nguyen |
| title_short | Totalsynthese von Ampullosporin und Analoga zur Ermittlung von morphogenen und neuroleptischen Struktur-Konformations-Wirkungs-Beziehungen |
| title_sort | totalsynthese von ampullosporin und analoga zur ermittlung von morphogenen und neuroleptischen struktur konformations wirkungs beziehungen |
| topic | Struktur-Aktivitäts-Beziehung (DE-588)4183784-8 gnd Ampullosporin A (DE-588)7516069-9 gnd Totalsynthese (DE-588)4412308-5 gnd |
| topic_facet | Struktur-Aktivitäts-Beziehung Ampullosporin A Totalsynthese Hochschulschrift |
| url | http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=014604836&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
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