Sequence-directed dynamics photophysical probes

Photophysical Probes of DNA Sequence-Directed Structure and Dynamics... 

PHOTOPHYSICAL PROBES OF DNA SEQUENCE-DIRECTED STRUCTURE AND DYNAMICS... 

The previous section illustrated the diversity of DNA sequence-directed structure and dynamics as assessed by many techniques, including NMR, crystallography, hydrodynamic and electrooptical methods, gel electrophoresis mobility and circularization studies, and scanning probe microscopies. Why then is it of interest to develop photophysical probes of such structures and dynamics, given the wealth of data that already exist The following arguments can be made (aside from pure scientific interest) ... 

There are, however, potential disadvantages to the use of photophysical probes in detecting sequence-directed DNA structure and dynamics. The probe molecule may require complicated synthesis or tedious incorporation into the DNA with subsequent purification the probe may introduce structural or dynamic distortions into the DNA. The first point has been well addressed for commonly used fluorescent probes such as fluorescein and tetramethylrhodamine, which are commercially available, and even oligonucleotides bearing such molecules in defined positions are commercially available. (It is also worth mentioning that some of the most informative NMR experiments rely on isotopic substitutions at the base or sugar, a challenging synthetic task as well.)... 

The second point is a fundamental property of the probe approach this issue is being addressed by designing probes that resemble as much as possible the native DNA base pairs. One can also make the argument that the use of an extrinsic probe such as an intercalator, which binds to DNA by insertion of a planar portion of itself into the base stack, is afunctional probe in the sense that the ability of unusual DNA structures/differentially flexible DNA sequences to bind to any molecule is a measurable parameter tied to the DNA function of being read, packaged, and unpackaged by external molecules. The principal photophysical methods to study DNA sequence-directed structure and dynamics are discussed in the following sections. 

C. J. Murphy, Photophysical probes of DNA sequence directed structure and dynamics Advances in... 

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