G-quadruplexes are four-stranded nucleic acid structures that exhibit extreme structural polymorphism. They are unique in that their formation is contingent on specific interactions with cations. G-quadruplexes can form intramolecularly or intermolecularly, depending principally on the primary sequence ofthe oligonucleotide(s). The polarity ofthe strands is also another form of classification. A G-quadruplex is said to be antiparallel when at least one strand is of opposite orientation in relation to the other three strands.

In this compilation ofmy work, I have studied the effects ofprimary sequence on the intramolecular folding of a G-quadruplexes arising from the Oxytricha nova telomeric sequence. The four-repeat ofthis particular sequence exhibits polymorphism depending on the type of cation present. In K+-containing solutions, two intramolecular G-quadruplexes are present. In the presence Na+, only a single antiparallel intramolecular G-quadruplex forms. By modifying the lengths ofthe G-tracts and those ofthe bases intervening between the G-tracts (loops), it became apparent that the structures that form deviate from the polymorphism exhibited by the natural four-repeat telomeric sequences. These results highlight the complexity ofpredicting the G-quadruplex topology a priori based on primary sequence. This information is an important addition to the limited amount of knowledge about the effects ofsequences on the resulting G-quadruplex structures arising from them.

Next, by using 7-deaza-8-aza guanine along with a novel Raman spectroscopy technique, I determined that DNA frayed wires, a set ofhighly thermostable DNA structures, are in fact G-quadruplexes. Furthermore, it was evident that a small portion ofDNA frayed wires are anti-parallel G-quadruplexes. By substituting each guanine with 8-bromo-guanine in d(A₁₅G₁₅), we identified a novel dimeric antiparallel G-quadruplex. To my knowledge, this is the first report ofsuch a G-quadruplex from a sequence having all its guanines replaced by 8- bromo-guanine.

Finally, based on the fact that DNA frayed wires are a set ofG-quadruplexes, I propose a simple method to control the polydispersity ofsuch structures. This technique takes advantage ofthe fact that different types of cations lead to different G-quadruplex conformations. Along with varying the cation type, temperature can be simultaneously manipulated to enhance the presence of certain species ofDNA frayed wires.