Design of ferrocene-peptide dimers for DNA binding and electrochemical sensing

Zhong, Xun (2014). Design of ferrocene-peptide dimers for DNA binding and electrochemical sensing. University of Birmingham. Ph.D.

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Abstract

GCN4 is a yeast transcriptional factor, which binds sequence selectively to DNA as a homodimer. Two domains are required to achieve this, an N-terminal basic domain, which interacts with the target site directly, and the C-terminal leucine zipper responsible for dimerisation. The latter can be replaced by chemically linking together two basic domains, to retain similar DNA binding. This work investigates using a ferrocene complex as the dimerization unit due to its flexibility and its characteristic electrochemical redox properties.

A strategy was proposed which took advantage of coupling to the thiol side chains of two cysteine residues, and detailed studies on dimerising two equivalents of Cys, or the tripeptide glutathione, were performed.

Design of five peptides based on GCN4, which were synthesized and dimerized with a ferrocene linker molecule, to combine the attractive redox electrochemistry of the stable ferrocene and the DNA binding ability of GCN4 dimerized basic domain. Molecular dynamic models were produced for four of the ferrocene peptide dimer complexes bound to target DNA over 10 ns. Their DNA binding ability was investigated by circular dichroism, and electrochemistry was studied in the absence and presence of non-specific and target DNA respectively.

Type of Work: Thesis (Doctorates > Ph.D.)
Award Type: Doctorates > Ph.D.
Supervisor(s):
Supervisor(s)EmailORCID
Peacock, AnnaUNSPECIFIEDUNSPECIFIED
Licence:
College/Faculty: Colleges (2008 onwards) > College of Engineering & Physical Sciences
School or Department: School of Chemistry
Funders: None/not applicable
Subjects: Q Science > QD Chemistry
Q Science > QH Natural history > QH426 Genetics
URI: http://etheses.bham.ac.uk/id/eprint/5242

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