Chemical mimics of the reverse turn structures in proteins have proven useful as therapeutics. This thesis describes the investigation of cyclic tetrapeptides (CTPs) which are found to be rigid and synthetically feasible turn mimics. CTPs rigidity were probed computationally and a few test examples made by solid phase peptide synthesis and then characterized by NOESY NMR. All reverse turns in the Protein Data Bank (PDB) were analyzed to determine conformational clustering based on the orientation of the four Cα-Cβ bonds. Combining the residues of glycine, L and D alanine, L and D proline, L and D N-methyl-alanine, and L and D pipecolic acid yielded a computational library of CTPs that mimicked over half the turns in the PDB, as determined by overlap of less than 0.65Å RMSD with the four Cα-Cβ bonds of each of 9 turn clusters.
|Advisor:||Marshall, Garland R.|
|School:||Washington University in St. Louis|
|School Location:||United States -- Missouri|
|Source:||DAI-B 69/09, Dissertation Abstracts International|
|Subjects:||Molecular biology, Biochemistry, Organic chemistry|
|Keywords:||Beta-turns, Cyclic tetrapeptides, Reverse turns, Tetrapeptides|
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