Item type:Thesis, Open Access

Synthesis and Analytics of Rigidified Peptide Architectures: Neuropeptide Y Dipeptide Scan, Ring-Chain-Equilibria of Iminopeptides, Thiazole Amino Acids for Thiopeptide Antibiotics

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Date

2010-10-13

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Philipps-Universität Marburg
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Abstract

The architectures (three-dimensional shapes) of peptides determine their respective biological functions. Therefore, the correct alignment of functionalities in a structure by constraining the flexibility is a key process in evolution as well as in medicinal chemistry in order to increase binding affinity and selectivity. The rigidification of a peptide chain can have local effects (incorporation of the amino acid proline) or it can globally restrain flexibility (macrocyclization). Furthermore, the combination of both strategies has given rise to complex antibiotics with highly optimized modes of action. This work approaches these principles in three topics and for different purposes. The first chapter presents a novel scanning strategy which utilizes synthetic local rigidifications for the evaluation of Neuropeptide Y structure and receptor binding patterns. The fundamental process of macrocyclization is topic of the second chapter. For iminopeptides, ring-chain equilibria can be established and controlled, thereby allowing for the thermodynamic analysis of the ring closure. This leads to the identification of structural determinants that influence the inclination of a peptide chain to close the ring. In the third chapter, a sugar-based synthetic pathway leading to highly functionalized thiazole dipeptides is described. This strategy led to the synthesis of core motivs of complex thiopeptide antibiotics, as well as to diastereomers and homologs thereof.

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Dates
Created: 2010Issued: 2010-10-13Updated: 2011-08-10
DOI
https://doi.org/10.17192/z2010.0564
Faculty
Fachbereich Chemie
Publisher
Philipps-Universität Marburg
Language
eng
Data types
DoctoralThesis
Keywords
MacrocyclisierungOrganic synthesisMacrocyclizationPeptide antibioticsThiazolesNMR spectroscopyVororientierungEntropiebilanz
DFG-subjects
NMR-SpektroskopieOrganische SyntheseScanningThiazolePeptidantibiotikum
DDC-Numbers
540
License
https://rightsstatements.org/vocab/InC-NC/1.0/
URI
https://open.uni-marburg.de/handle/10.17192/z2010.0564
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Enck, Sebastian (133170888): Synthesis and Analytics of Rigidified Peptide Architectures: Neuropeptide Y Dipeptide Scan, Ring-Chain-Equilibria of Iminopeptides, Thiazole Amino Acids for Thiopeptide Antibiotics. : Philipps-Universität Marburg 2010-10-13. DOI: https://doi.org/10.17192/z2010.0564.

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