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Title: G-quadruplex recognition and isolation with small molecules
Author: Mûller, Sebastian
ISNI:       0000 0004 2707 8975
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2011
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An increasing interest in non-canonical nucleic acid structures has drawn the attention of the scientific community during the last few decades. One such structure, the G-quadruplex, has been the focus of an increasing number of scientists as G-quadruplexes are believed to play a role in biological processes such as telomere integrity and gene expression. Their existence in vivo is largely unproven but they have stimulated a lot of research into small molecules that interact with them. The development of a new class of such molecules is described in this thesis. A member of this family showed to be very selective in stabilising one particular G-quadruplex. The further development of another family of G-quadruplex interacting small molecules is also presented in this thesis and some of their effects in cellulo were assessed. Based on the scaffold of this family, an affinity probe was developed, which can mediate the isolation of its nucleic acid targets from human cells. This is the first example of the use of a small molecule with an affinity tag that has been used to isolate a nucleic acid target in a structure specific manner from human cells.
Supervisor: Balasubramanian, Shankar Sponsor: Cancer Research UK
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
Keywords: Small molecule ; G-quadruplex ; Pull-down ; Isolation ; DNA