Towards artificial metalloenzymes: synthesis of non-natural amino acids

Almeida, Ana I. O. (2021). Towards artificial metalloenzymes: synthesis of non-natural amino acids. University of Birmingham. Ph.D.

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Abstract

Enzymes are Nature’s catalysts known for their high selectivity, turnoverrates, stereocontrol, low catalyst loading and water solubility. For years
researchers have striven to bring some of these features into small moleculecatalysis. Chemoenzymatic synthesis is a growing field that utilizes natural proteins to perform organic transformations. However, use of natural proteins is not straightforward due to their high sensitivity to pH and temperature changes, which together with their specificity does limit substrate scope. Recent efforts combine synthetic peptide scaffolds with non-biological transition metals to prepare artificial enzymes. One can expect that a structured peptide could provide a chemo- and stereoselective environment, capable of behaving in an enzyme-like manner.

The amino acid toolbox available to nature is restricted to twenty commonly available side chains, which are limited regarding their transition metal coordination abilities. In order to move towards artificial enzymes and expand the potential of metal coordination onto peptides, novel non–natural amino acids containing ligand side chains are required.

In this work, amino acid feedstocks were successfully converted into imidazolium and phosphorous ligands for transition metals. Gold and palladium metals complexes bearing amino acid side chains were synthesized and the catalytic activity of the gold complexes was tested in the regioselective hydration of alkynes and cycloisomerization of enynes reactions. These amino acids have been successfully used in solid phase peptide synthesis including in the preparation of structured peptides.

Type of Work: Thesis (Doctorates > Ph.D.)
Award Type: Doctorates > Ph.D.
Supervisor(s):
Supervisor(s)EmailORCID
Davies, PaulUNSPECIFIEDUNSPECIFIED
Peacock, AnnaUNSPECIFIEDUNSPECIFIED
Licence: All rights reserved
College/Faculty: Colleges (2008 onwards) > College of Engineering & Physical Sciences
School or Department: School of Chemistry
Funders: Engineering and Physical Sciences Research Council
Subjects: Q Science > QD Chemistry
URI: http://etheses.bham.ac.uk/id/eprint/11439

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