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Stereochemically Modified Polyamides for Recognition in the Minor Groove of DNA


Herman, David Matthew (2001) Stereochemically Modified Polyamides for Recognition in the Minor Groove of DNA. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/vsf2-fe75.


The design of synthetic molecules that recognize specific sequences of DNA is an ongoing challenge in molecular medicine. Cell-permeable small molecules targeting predetermined DNA sequences offer a potential approach for offsetting the abnormal effects of misregulated gene-expression. Over the past twenty years, Professor Peter B. Dervan has developed a set of pairing rules for the rational design of minor groove binding polyamides containing pyrrole (Py), imidazole (Im), and hydroxypyrrole (Hp). Polyamides have illustrated the capability to permeate cells and inhibit transcription of specific genes in vivo. This provides impetus to identify structural elements that expand the repetoire of polyamide motifs with recognition properties comparable to naturally occurring DNA binding proteins. Through the introduction of chiral amino acids, we have developed chiral polyamides with stereochemically regulated binding characteristics. In addition, chiral substituents have facilitated the development of new polyamide motifs that broaden binding site sizes targetable by this class of ligands.

Item Type:Thesis (Dissertation (Ph.D.))
Subject Keywords:Biochemistry and Molecular Biophysics
Degree Grantor:California Institute of Technology
Major Option:Biochemistry and Molecular Biophysics
Thesis Availability:Public (worldwide access)
Research Advisor(s):
  • Hoffmann, Michael R.
Thesis Committee:
  • Parker, Carl Stevens (chair)
  • Dervan, Peter B.
  • Mayo, Stephen L.
  • Hsieh-Wilson, Linda C.
  • Hoffmann, Michael R.
Defense Date:22 February 2001
Record Number:CaltechTHESIS:03122014-104807866
Persistent URL:
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:8130
Deposited On:12 Mar 2014 18:23
Last Modified:13 Sep 2022 18:43

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