| dc.contributor.advisor | Diederichsen, Ulf Prof. Dr. | |
| dc.contributor.author | Pahlke, Denis | |
| dc.date.accessioned | 2019-07-31T08:07:49Z | |
| dc.date.available | 2019-07-31T08:07:49Z | |
| dc.date.issued | 2019-07-31 | |
| dc.identifier.uri | http://hdl.handle.net/21.11130/00-1735-0000-0003-C180-1 | |
| dc.identifier.uri | http://dx.doi.org/10.53846/goediss-7587 | |
| dc.language.iso | eng | de |
| dc.publisher | Niedersächsische Staats- und Universitätsbibliothek Göttingen | de |
| dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | |
| dc.subject.ddc | 540 | de |
| dc.title | Synthesis, characterisation and sensor-functionalisation of transmembrane β-peptides | de |
| dc.type | doctoralThesis | de |
| dc.contributor.referee | Diederichsen, Ulf Prof. Dr. | |
| dc.date.examination | 2018-12-13 | |
| dc.description.abstracteng | Membrane proteins represent an important class of proteins as they are encoded in up to 30 % of the open reading frame. More than 50 % of currently available drugs target membrane proteins, emphasising the importance of membrane protein research. A large number of complex membrane proteins consist of the well-known ɑ-helices. Therefore, different peptidomimetics have been developed to imitate the behaviour and function of ɑ-helical transmembrane proteins in a less complex environment. Besides the use of transmembrane ɑ-peptides, the design and synthesis of further transmembrane model systems based on artificial β-peptides consisting of β-amino acids has become of great interest. The development of model transmembrane β-peptides can help to understand the orientation or the peptide aggregation of helical transmembrane peptides and proteins.
The first part of this thesis focuses on the synthesis, characterisation and investigation of transmembrane β-peptides which were inspired by prior studies. These novel transmembrane β-peptides differ in the N-terminal modification and partially in the peptide length, which extend range of transmembrane β-peptides. Their secondary structure was analysed in organic solvents as well as in large unilamellar vesicles by means of circular dichroism spectroscopy. Furthermore, membrane insertion was investigated by tryptophan fluorescence spectroscopy. Therefore, D-β3-homotryptophan (D-β3-hTrp) was inserted either peripherally or centrally into the hydrophobic peptide sequence to observe the tryptophan fluorescence which is influenced by the surrounding polarity.
The second part of this thesis deals with the question whether β-peptides can function as membrane-anchored molecular rulers to investigate processes at the membrane interface. Hence, the advantages of β-peptides like conformationally well defined and stable secondary helix structures seem to be interesting for the development of new transmembrane anchoring peptides. Recently published transmembrane β peptides were equipped either with a pH sensor (carboxyfluorescein) or with a newly designed Ca2+ sensor. To analyse near membrane pH values, two carboxyfluorescein labelled transmembrane β-peptides were synthesised with different sensor distances to the membrane surface and pH titration was employed. The different distances were achieved by attaching the sensor to peptides with varying lengths of the peptide sequence outside the membrane. To analyse near membrane Ca2+ concentration, two Ca2+ sensors were developed based on literature known models. | de |
| dc.contributor.coReferee | Steinem, Claudia Prof. Dr. | |
| dc.subject.eng | Transmembrane β-Peptides | de |
| dc.subject.eng | Solid Phase Peptide Synthesis (SPPS) | de |
| dc.subject.eng | Circular Dichroism (CD) Spectroscopy | de |
| dc.subject.eng | Fluorescence Spectroscopy | de |
| dc.subject.eng | β-Amino Acids | de |
| dc.subject.eng | Ca2+ sensors | de |
| dc.subject.eng | pH sensors | de |
| dc.subject.eng | Automatic Solid Phase Peptide Synthesis | de |
| dc.identifier.urn | urn:nbn:de:gbv:7-21.11130/00-1735-0000-0003-C180-1-2 | |
| dc.affiliation.institute | Fakultät für Chemie | de |
| dc.subject.gokfull | Chemie (PPN62138352X) | de |
| dc.identifier.ppn | 1672307082 | |