Sterochemically modified polyamides for recognition in the minor groove of DNA

Biochemistry and Molecular Biophysics

Herman, David Matthew ; Dervan, Peter B.

University:California Institute of Technology

Department:Biology

关键词: Biochemistry and Molecular Biophysics;   

Others  :  https://thesis.library.caltech.edu/8130/7/Herman%202001.pdf

美国|英语

来源: Caltech THESIS

【 摘 要 】

The design of synthetic molecules that recognize specific sequences of DNAis an ongoing challenge in molecular medicine. Cell-permeable small moleculestargeting predetermined DNA sequences offer a potential approach for offsettingthe 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 designof minor groove binding polyamides containing pyrrole (Py), imidazole (Im), andhydroxypyrrole (Hp). Polyamides have illustrated the capability to permeate cellsand inhibit transcription of specific genes in vivo. This provides impetus to identifystructural elements that expand the repetoire of polyamide motifs with recognitionproperties comparable to naturally occurring DNA binding proteins. Through theintroduction of chiral amino acids, we have developed chiral polyamides withstereochemically regulated binding characteristics. In addition, chiral substituentshave facilitated the development of new polyamide motifs that broaden binding sitesizes targetable by this class of ligands.