| dc.contributor.advisor | Diederichsen, Ulf Prof. Dr. | |
| dc.contributor.author | Kugler, Benedikt | |
| dc.date.accessioned | 2021-08-16T10:51:51Z | |
| dc.date.available | 2021-08-22T00:50:03Z | |
| dc.date.issued | 2021-08-16 | |
| dc.identifier.uri | http://hdl.handle.net/21.11130/00-1735-0000-0008-58DE-C | |
| dc.identifier.uri | http://dx.doi.org/10.53846/goediss-8781 | |
| 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 | Investigation of Peptidic Templates for Bioorthogonal Ligations | de |
| dc.type | doctoralThesis | de |
| dc.contributor.referee | Diederichsen, Ulf Prof. Dr. | |
| dc.date.examination | 2021-04-13 | |
| dc.description.abstracteng | One of the biggest challenges for biochemical researchers in the postgenomic era remains the elucidation of structure-activity relationships in proteins. While many proteins can be routinely produced by recombinant protein expression and studied in a controlled environment, post-translational modifications, such as acylation, methylation, phosphorylation, lipidation, prenylation, ubiquitination, or glycosylation are additionally required to reproduce the diversity found in nature. Traditionally, these modifications have been carried out by targeting nucleophilic amino acid side chains. This process frequently results in a heterogeneous product distribution. The discovery of additional methods for the chemoselective modification of proteins, as well as the scope expansion of currently existing methodology is therefore worth investigating. Within the scope of this thesis, fundamental research on the application and effect of templates for protein labeling is conducted. A long-term research goal in our workgroup is the development of a method to simultaneously introduce two protein modifications, while maintaining site selectivity. Our approach in reaching this goal is based on the use of peptide templates to facilitate the labeling reaction at low concentrations by increasing the effective molarity of the reactants. The sequence specificity of the template is furthermore responsible for ensuring site-selectivity. Introduction of photocleavable linkers between the template strands and tags aid in the (partial) removal of the reaction scaffold after transfer of the label to the target protein. Based on previous work in our group, photocleavable peptide nucleic acid templates are investigated with respect to their orthogonality. To extend the scope of this method, the template’s ability to enhance a cross-coupling reaction is explored. Finally, coiled-coil peptides are investigated as templates because of the additional layer of orthogonality they provide in terms of recognition and site-selectivity and their standalone ability to serve as a platform for stoichiometric bioconjugations at low concentrations. | de |
| dc.contributor.coReferee | Alcarazo, Manuel Prof. Dr. | |
| dc.contributor.thirdReferee | Bennati, Marina Prof. Dr. | |
| dc.contributor.thirdReferee | Tittmann, Kai Prof. Dr. | |
| dc.contributor.thirdReferee | Frauendorf, Holm Dr. | |
| dc.contributor.thirdReferee | John, Michael Dr. | |
| dc.subject.ger | Solid phase peptide synthesis | de |
| dc.subject.eng | Peptide nucleic acid | de |
| dc.subject.eng | Bioorthogonal | de |
| dc.subject.eng | Ligation | de |
| dc.subject.eng | Template reaction | de |
| dc.subject.eng | Photocleavable linker | de |
| dc.subject.eng | Coiled coil | de |
| dc.identifier.urn | urn:nbn:de:gbv:7-21.11130/00-1735-0000-0008-58DE-C-6 | |
| dc.affiliation.institute | Fakultät für Chemie | de |
| dc.subject.gokfull | Chemie (PPN62138352X) | de |
| dc.description.embargoed | 2021-08-22 | |
| dc.identifier.ppn | 1767138512 | |