(Georgia Institute of Technology, 2010-11-18)
Chen, Michael
Individuals suffering from Friedrich’s ataxia, a neuromuscular hereditary disease, have expansions of the DNA triplet repeat GAA/TTC in their genomic DNA. Preliminary investigations into the disease point to the ability of triplet repeats to adopt unusual DNA structures, such as matched and mismatched triplexes. This paper presents a novel method to probe the secondary structure of nucleic acids with the binding specificity of ligands called intercalators. In previous studies, the type of nucleic acid structure an intercalator binds to is dependent on the chemical identity and molecular shape of the intercalator. Using this selectivity, azacyanines “shown to target the in vivo structure that GAA/TTC triplet repeats form” will be combined with nucleic acids of various known structures. The nucleic acid structure that azacyanine has the highest affinity for will most likely be the structure of the GAA/TTC triplet repeat. The discovery of the structure that causes DNA triplet repeat disorders could lead to the development of novel therapeutic treatments.
(Georgia Institute of Technology, 2009-11-09)
Chen, Michael
In recent years, the RNA-world hypothesis has become the leading theory for the origins of life. Few researchers, though, believe RNA could have spontaneously appeared out of the primordial soup.
Regardless of the speculation about what could have preceded RNA, any origins of life theory would
have one seemingly insurmountable obstacle: strand cyclization. Due to the flexibility of RNA-like or
DNA-like polymers, a strand growing in solution would not grow much longer than 4 units, which is a problem because genes are usually hundreds, if not thousands, of units long. However,
intercalator "planar molecules that slip between base pairs" increase the stiffness of the polymer
thereby promoting linear growth. Using tetra-nucleotides as the model system and varying
intercalators, we show that intercalators are the solution to strand cyclization.