Raman probes for different DNA structures
Date Issued
2009
Date
2009
Author(s)
Fang, Hung-Chih
Abstract
At the end of 80s, scientists realized that the end of eukaryotic chromosomes contain G-rich single-stranded DNA, telomere. These telomeres could adopt novel secondary structures, termed G-quadruplexes. Also, quadruplex-folded telomeric DNA has been found related to cancer activity. Recently, G-quadruplexes at non-telomeric sites were also detected, especially in promoter regions of proto-oncogene. These findings inspired scientists to get more involved in G-quadruplexes research. Some scientists aim to discover small molecules for stabilization of G-quadruplex structure that could potentially lead to cancer therapeutic drugs.n this work, we study the binding modes of G-quadruplex stabilizers and develop molecular probes that can recognize different DNA structures. First, we compare the binding affinity, between carbazole derivative (BMVC-4) and diphenylamine derivative (BMVPA-4) with G-quadruplex by using absorption, fluorescence, circular dichroism spectra and gel electrophoresis experiments. We found the rigid carbazole structure could stabilize G-quadruplex DNA more ffectively than flexible diphenylamine structure.urthermore, owing to the low intrinsic fluorescence intensity of BMVC-4 and BMVPA-4, we could obtain the Raman spectra through resonance Raman, and do the vibrational mode assignments to identify the functional group which is mainly used to interact with DNA. The shifts of Raman lines imply the interaction of BMVC-4 to G-quadruplex is larger than that to duplex DNA while BMVPA-4 show the opposite interaction. So, BMVC-4 and BMVPA-4 could cooperate in DNA structure recognition. In addition, since BMVPA-4 is more flexible than BMVC-4, it is more sensitive to DNA structure differences, especially in investigating the variations of bcl2mid and bcl2mid-M (two bases mutant of bcl2mid). Also, our results implicate AT loci as the primary sites of BMVPA-4 intercalation. Therefore, we suggest that BMVPA-4 is a better Raman probe for DNA structure recognition.ased on these works, we could not only extend the application of Raman probes, but also provide information to drug design of DNA stabilizers in the future.
Subjects
G-quadruplex
carbazole
diphenylamine
Raman probe
SDGs
Type
thesis
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