Solid phase synthesis of DNA-binding small molecules

• Main Author: Baird, Eldon Eugene
• Format: Others
• Language: en
• Published: 1999
• Online Access: https://thesis.library.caltech.edu/1532/1/Baird_ee_1999.pdf; Baird, Eldon Eugene (1999) Solid phase synthesis of DNA-binding small molecules. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/zky0-ha94. https://resolver.caltech.edu/CaltechETD:etd-04282006-113514 <https://resolver.caltech.edu/CaltechETD:etd-04282006-113514>

Small molecules that bind to any predetermined DNA sequence in the human genome are potentially useful tools for molecular biology and human medicine. A twenty year research effort led by Dr. Peter B. Dervan at the California Institute of Technology has led to the development of "pairing rules" to control rationally the sequence-specificity of polyamides that bind in the DNA minor groove. During the course of my Ph.D. research, methodology was developed for the machine-assisted solid phase synthesis of these DNA-binding polyamides (Chapter 2). The large number of polyamides made available by the solid phase synthetic methodology has greatly accelerated the development of this class of molecules. Polyamides prepared by solid phase synthetic methodology have been used by a variety of collaborators to: extend the targetable binding-site size (Chapter 3), recognize predetermined DNA sequences with subnanomolar affinity (Chapter 6), regulate gene expression in human cells (Chapter 7), and recognize all four base pairs in the DNA minor groove (Chapter 8).