β-Turns jenseits natürlicher Limitierungen - Flexible und rigide Dipeptidbausteine in der Proteinumgebung des Foldon-Trimers und seinem isolierten b-hairpin

β-turns vermitteln eine Vielzahl unterschiedlicher Protein-Erkennungsprozesse im menschlichen Organismus, obwohl die Torsionswinkelpräferenzen der kanonischen Aminosäuren die zugänglichen b-turn-Geometrien und -Beweglichkeit einschränken. Die organische Chemie kann diese Limitierungen überschreiten:...

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Bibliographic Details
Main Author: Körling, Matthias
Contributors: Geyer, Armin (Prof. Dr.) (Thesis advisor)
Format: Doctoral Thesis
Language:German
Published: Philipps-Universität Marburg 2015
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β-turns mediate diverse protein recognition processes in the human organism, although dihedral angle preferences of canonical amino acids limit accessible β-turn geometries and their mobility. Organic chemistry can go beyond these limitations: Synthetic b-turn dipeptide building blocks with more flexible or rigid backbones outpace the characteristics of canonical amino acids. That leads to significantly altered populations of the natural stand-alone hairpin (Ala12–Ser24) derived from the Foldon miniprotein due to their differing turn inducing capacities. The influence of the same β-turn mimetics on the b-hairpin was also studied within the complex protein environment of the trimeric Foldon by analyzing several NMR based parameters and their melting tempera-tures. In contrast to the isolated b-hairpin, for which rigid β-turn mimetics in the i+1 and i+2-turn positions lead to highly populated folds, the best combinations to fulfill the structural and dy-namical requirements of the Foldon protein-protein interfaces between the monomer chains are natural b-amino acids. The obtained data raises questions on whether highly stabilized, designed b-hairpins are suitable as b-sheet model systems to simulate evolutionarily optimized proteins in a complete fashion, especially in their dynamic behavior.