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Recently, Zhang Sodium, a researcher at the Center for Strong Magnetic Field Science at hefei Material Science Institute of the Chinese Academy of Sciences, used nuclear magnetic resonance (NMR) technology to analyze the intermolecular V-shapeD G-tetra-chain composite structure formed by the telomere DNA sequence d (G2T4G4T4G4) and the short-chain d (TG4A) probe for the first time, and found that the new short-chain DNA probe can specifically identify the telomere sandaldna containing V-shape key base sequence.
the findings were published online in the international journal Nucleic Acids Research (doi: 10.1093/nar/gky1167).
telomere DNA formation of G-tetrachain structure is closely related to cancer inhibition, is an excellent anti-cancer target.
G-quad chain, in addition to the classic connecting ring area, there is a unique V-shaped bracket structure domain, which does not contain any intermediate residues, but can span three G-quadplane planes.
this V-shaped bracket can make a sharp reversal of the direction of the glycophosphate skeleton chain between the two adjacent bases, while participating in the formation of the G-quadrine core of the hydrogen bond connection.
these properties make the V-stent itself different, making it inherently more easily specifically identified as a drug design target.
telomere DNA is composed of repetitive base sequence units, which results in it being identified by traditional antisense complementary chain probes, which is usually not ideal.
, Zhang sodium team predicted that as an alternative method of traditional antisense complementary chains, two different DNA oligomers were able to form G-quadrines between molecules, in which longer DNA oligomers were targeted by short G-rich DNA probe fragments, which in turn helped to identify the repeated structural sequences rich in continuous G sequences in telomere DNA.
however, the structure of the V-shaped G-quad chain, which consists of different lengths of DNA oligomers, has not been reported.
in this work, the researchers first analyzed the liquid NUCLEAR magnetic resonance structure of the tepsomatic sequence d (G2T4G4T4G4G4) and probe d (TGGGGA) of the sharp caterpillar, proving that the compound is a new type of asymmetrical molecule V-shaped G-tetra-chain.
through the competitive combination experiment of mr. imrion, it is found that the thermodynamics are more stable and the dynamics form are faster than the conventional G-quad-chain configuration.
follow-up researchers further treated the base mutation of the original sequence, which proved that in the natural mutants of human-derived telomere DNA, as long as the sequence with the characteristics of d (G2NG3NG4) was obviously easier to identify and capture by the probe than other sequences, thus providing a new way of thinking and theoretical support for the target probe design of the anti-cancer target telomerase DNA region.
the research work was completed by the first author of the paper, postdoctoral wan Wei, as well as doctoral students Fu Wenqiang, Jing Haitao, communication author Zhang Sodium and others.
the research was supported by the National Natural Science Foundation of China Youth Science Foundation, the National Natural Science Foundation of China, the National Key Research and Development Program, etc.
the work of mr. mr. magnetic resonance is carried out on the stable-state strong magnetic field experimental device.
Source: Hefei Institute of Physical Sciences.