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Title: Development of optical probes and redox-activated complexes as G-quadruplex binders
Author: Bandeira Pedro De Farias, Stephane
ISNI:       0000 0004 7657 6997
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2017
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Guanine-rich oligonucleotides can form non-canonical secondary structures that are referred to as G-Quadruplex and are present not only in the telomeres but also in promotor regions of some oncogenes. Due to their biological relevance, G-Quadruplexes are attractive targets for small molecules design. The research presented in this thesis aimed (i) to design and synthesize for the first time a platinum(IV) salphen complex featuring two chlorides at the axial positions, which could be switched on/off upon reduction using bio-reducing agents, thus rendering a good G4 binder; (ii) to create a dyad system featuring a fluorescent NBD moiety and Ni salphen, in order to achieve fluorescence quenching of the NBD moiety in the absence of G-Quadruplex DNA, for an "on-off" effect; and (iii) to design a bimetallic complex, and to attempt its synthesis. The interaction between the metal complexes and G-quadruplex DNA was examined by means of circular dichroism (CD), fluorescence and UV-vis titrations.
Supervisor: Vilar Compte, Ramon Sponsor: Conselho Nacional de Desenvolvimento Científico e Tecnológico
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral