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The molecular recognition of DNA by novel heterocycles

Citation

Marques, Michael Anthony (2005) The molecular recognition of DNA by novel heterocycles. Dissertation (Ph.D.), California Institute of Technology. http://resolver.caltech.edu/CaltechETD:etd-05252005-143409

Abstract

With a rapid movement toward personalized genetic medicine, tailoring treatment to individual patient needs based on their genetic code is becoming an important goal. The ability to develop small molecules capable of reprogramming the cellular machinery at the genetic level is one approach to the difficult challenge of treating diseases that result from aberrant gene expression. Inspired by the architecture of the natural products netropsin and distamycin, polyamides are capable of binding the DNA minor groove with high affinity and fidelity. Originally composed of five-membered heterocyclic carboxamides, polyamides have evolved in both form and function. A search has been initiated to develop new DNA specific oligomers that have different electronic and geometric properties. Alteration of these properties may lead to a new class of compounds, capable of targeting DNA sequences that have previously been shown to be difficult to recognize. Second-generation compounds containing novel heterocyclic recognition elements, within the context of both 5-membered heterocyclic carboxamides and fused 6-5 benzimidazole analogues, have recently been developed. These molecules have successful DNA recognition profiles as well as favorable cell uptake properties, important considerations when searching for effective pharmacophores. These new classes of rationally designed oligomers offer one approach to the challenging problem of regulating gene expression.

Item Type:Thesis (Dissertation (Ph.D.))
Subject Keywords:DNA; Heterocycles; Molecular Recognition; Oligomers; Polyamides
Degree Grantor:California Institute of Technology
Division:Chemistry and Chemical Engineering
Major Option:Chemistry
Thesis Availability:Public (worldwide access)
Research Advisor(s):
  • Dervan, Peter B.
Thesis Committee:
  • Stoltz, Brian M. (chair)
  • Hsieh-Wilson, Linda C.
  • Dervan, Peter B.
  • Mayo, Stephen L.
Defense Date:13 May 2005
Author Email:Marques (AT) caltech.edu
Record Number:CaltechETD:etd-05252005-143409
Persistent URL:http://resolver.caltech.edu/CaltechETD:etd-05252005-143409
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:2053
Collection:CaltechTHESIS
Deposited By: Imported from ETD-db
Deposited On:26 May 2005
Last Modified:26 Dec 2012 02:46

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