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Targeting repeat sequences with DNA-binding small molecules

Citation

Chevillet, John Richard (2002) Targeting repeat sequences with DNA-binding small molecules. Master's thesis, California Institute of Technology. http://resolver.caltech.edu/CaltechTHESIS:02022012-110126423

Abstract

Recognition of repeat sequences in DNA would have applications in molecular biology. One of the most biologically interesting repeat sequences is the telomeric repeat which composes the ends of eukaryotic chromosomes; in vertebrates 5'-TTAGGG-3'. This sequence has been used as a model to study how DNA-binding polyamide molecules composed of pyrrole (Py) and imidazole (Im) residues bind to repeating sequences. DNase I footprinting shows that the polyamide-fluorophore conjugate IrnImImPy-γ-PyPy((CH_2)_3N,N',N''trimethylbis hexamethylene)triamineOregonGreen488) PyPy-β-Me can bind the sequence 5'-AGGGTT-3' K_a = 1.8x10^8 M^(-1). Quantitative fluorescence titrations with varying patterns of telomeric repeat suggest that the molecule can tolerate another polyamide binding contiguously, but not two. Truncation of the tail of the conjugate to yield the molecule ImImImPy-γ-Py Py((CH_2)_3N,N',N''trimethylbis (hexamethylene)triamine-OregonGreen488) PyPy-Me allows the compound to bind three contiguous sites, suggesting that steric polyamide-polyamide interactions control binding in this manner.

Item Type:Thesis (Master's thesis)
Subject Keywords:Chemistry
Degree Grantor:California Institute of Technology
Division:Chemistry and Chemical Engineering
Major Option:Chemistry
Thesis Availability:Restricted to Caltech community only
Research Advisor(s):
  • Unknown, Unknown
Thesis Committee:
  • Unknown, Unknown
Defense Date:1 January 2002
Record Number:CaltechTHESIS:02022012-110126423
Persistent URL:http://resolver.caltech.edu/CaltechTHESIS:02022012-110126423
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:6806
Collection:CaltechTHESIS
Deposited By: Benjamin Perez
Deposited On:03 Feb 2012 15:59
Last Modified:26 Dec 2012 04:40

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