Synthesis of guanidine amino acids and investigation of their interactions with nucleic acid

Möschwitzer, Vicki Doreen 2011. Synthesis of guanidine amino acids and investigation of their interactions with nucleic acid. PhD Thesis, Cardiff University. Item availability restricted.

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Abstract

Certain amino acids have a high propensity to be found at the intermolecular contact regions in protein-nucleic acid complexes. One of them is arginine whose side chain commonly makes contact through electrostatic interactions with phosphates and hydrogen bonding to nucleobases. Rigidified arginine analogues in which the side chain is cyclised would reduce torsional entropy loss occurring on binding. In this project amino acids were synthesised with cyclic guanidine side chains as modular arginine analogue building blocks for preparation of nucleic acid binding peptides. The synthetic strategies to prepare the amino acids involve Grignard reactions and Heck coupling reactions with iodo-pyrimidines. The Heck coupling is followed by a catalytic asymmetric hydrogenation to generate the stereo centre. An enzymatic kinetic resolution is essential after the Grignard coupling to provide stereoselectivity. Small molecule interactions with nucleic acids can be used as a tool for modulating processes like transcription and translation. Ultimately peptide binding screens against the mRNA of TGF-β1 may be undertaken to study the role of protein binding in regulation of translation. Within this thesis a peptide library was prepared via the split and recombine method using macro-beads which provides valuable groundwork for the aim of continuing research. This would be the synthesis of peptides containing rigidified arginine mimetics that interact with mRNA of TGF-β1 or other nucleic acids.

Item Type:	Thesis (PhD)
Status:	Unpublished
Schools:	Chemistry
Subjects:	Q Science > QD Chemistry
Funders:	EPSRC
Date of First Compliant Deposit:	30 March 2016
Last Modified:	19 Mar 2016 23:18
URI:	https://orca.cardiff.ac.uk/id/eprint/46436

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