Programmable Oligomers for DNA Recognition

• Main Author: Doss, Raymond Michael
• Format: Others
• Published: 2006
• Online Access: https://thesis.library.caltech.edu/3672/1/Doss_rm_2006.pdf; Doss, Raymond Michael (2006) Programmable Oligomers for DNA Recognition. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/F0X3-Q612. https://resolver.caltech.edu/CaltechETD:etd-09202008-110622 <https://resolver.caltech.edu/CaltechETD:etd-09202008-110622>

<p>As the amount of information about the genetic construct of the human body continues to grow, the ability to manipulate genes via the use of synthetic molecules becomes an increasingly attractive concept. Polyamides developed in the Dervan Lab are capable of doing just this by binding in the minor groove of DNA in a highly specific manner. Not only are polyamides able to specifically target sequences of DNA, but they are able to do so at affinities which make them competitive with endogenous transcriptional machinery.</p> <p>The complex nature of the DNA minor groove structure, however, has forced the evolution of traditional imidazole, pyrrole and hydroxypyrrole polyamides into newly developed oligomers — compounds which have been shown to bind sequences of DNA that have been traditionally difficult to target. In going from polyamides to oligomers, these compounds have seen a variety of changes brought about by the search for ring systems capable of conveying improved binding properties. Several new recognition elements have been uncovered and characterized with respect to their DNA affinity and specificity. Experiments testing the capabilities of these oligomers have shown that such compounds demonstrate great potential for targeting many new, biologically relevant sequences of DNA thus showing promise as potential 2nd generation therapeutics.</p>