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Structural modifications to DNA-binding polyamides for improved biological activity in cell culture

Citation

Jacobs, Claire Sigrid (2009) Structural modifications to DNA-binding polyamides for improved biological activity in cell culture. Dissertation (Ph.D.), California Institute of Technology. http://resolver.caltech.edu/CaltechETD:etd-05272009-161836

Abstract

Polyamides are a class of synthetic small molecules that recognize DNA in a sequence-specific fashion through a network of hydrogen bonds formed with bonding partners in the floor of the minor groove. The binding affinity of polyamides is comparable to that of numerous DNA-binding proteins, and polyamides have been shown to displace DNA-binding proteins. As such, they present a powerful opportunity to modulate expression levels of genes vital to human health. The cellular permeability and biological activity of polyamides has presented an impediment in moving from in vitro to in vivo work that was partially removed by the discovery that fluorescein dyes facilitate cell entry. The work described here details recent advances in modifications to the C-terminal polyamide linker, linkage and tail groups that improve the endogenous inducible gene regulation activity of polyamides in cell culture.

Item Type:Thesis (Dissertation (Ph.D.))
Subject Keywords:ARE; Gene regulation; HIF; Polyamide; PSA; VEGF
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:
  • Bercaw, John E. (chair)
  • Stoltz, Brian M.
  • Rees, Douglas C.
  • Dervan, Peter B.
Defense Date:6 March 2009
Record Number:CaltechETD:etd-05272009-161836
Persistent URL:http://resolver.caltech.edu/CaltechETD:etd-05272009-161836
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1021/jm900256fDOIUNSPECIFIED
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:2181
Collection:CaltechTHESIS
Deposited By: Imported from ETD-db
Deposited On:02 Jun 2009
Last Modified:26 Dec 2012 02:48

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