Conformational analysis of 4-azidoproline derivatives and their application in molecular recognition

This thesis presents studies on the influence of 4-azido-substitutents in azidoproline on the
conformation of the pyrrolidine ring system as well as the conformation around the peptide
bond in acetylated monomers and dimers. The azido-group may be reduced to an amine,
which allows for further modifications. The insights gained were applied to the synthesis of a
tripodal molecular scaffold. This scaffold was used as a backbone for a synthetic receptor,
which binds peptides in aqueous solution.
In the first part of this thesis the effect of the azido-substituent on the conformation of
4-azidoproline is described. By NMR-spectroscopy, X-ray diffraction, FT-IR spectroscopy
and ab initio calculations, the conformation of 4-azidoproline derivatives was analyzed.
Particular focus was laid on the s-cis:s-trans ratio and the factors influencing it. Furthermore,
the kinetics of the interconversion of the s-cis and s-trans conformation of diastereomeric
4-azidoproline derivatives were determined by EXSY-NMR.
The second part of this thesis describes the synthesis and structural analysis of the
azido-functionalized cyclotriproline and its application as a molecular scaffold for a peptide
receptor. The binding properties were analyzed in on-bead screenings against an encoded
tripeptide library in different buffer solutions. The binding affinity to a selected peptide was
measured by isothermal titration calorimetry (ITC).