Synthesis Of The Azobenzene Derivatives And The Studies Of Conformational Photoregulation Of Telomere DNA D (TTAGGG)₄

The maintenance of chromosomes is influenced by telomeres, which further affects the life of cells and they are closely linked with some factors of human health such as the ageing, cancer, and so on. Meanwhile, the telomeric G-quardruplex structure plays an important role in the performance of telomeres. As a result, it is very important to study the conformational regulation of telomeric G-quardruplex. Among various kinds of methods, photoregulation is the most popular since it is the cleanest source of energy and can be recycled. Among the candidates, azobenzene moiety has received considerable attention due to its reversible photoisomerization property, and recently it is widely used in the research of photoregulation of DNA.In this thesis, four azobenzene derivatives 1,2,3,4 were designed and synthesized, which were fully characterized by NMR spectroscopy and HRMS methods. And their particular properties of photoisomerization were demonstrated by UV/Vis spectroscopy and 1H NMR. Then, their activities of photoregulating the conformation of telomeric G-quardruplex were mainly studied.Firstly, we did our research in the absence of potassium or sodium ions. CD spectroscopy, exonuclease I hydrolysis assay,'H NMR and calculations of the corresponding molecular-modeling were performed to demonstrate the conformational photoregulation. Thermal denaturation studies and UV/Vis-absorption titration experiments were performed to evaluate the stabilization of the formed G-quadruplexes and the equilibrium binding constants of compounds and G-quadruplexes. Next, we evaluated the performances in the presence of potassium or sodium ions. Then, we further studied the systerm in the mimic molecular crowding conditions.The results showed that the synthesized azobenzene derivatives can reversibly stretch and fold the structure of G-quadruplexes in the absence of potassium or sodium ions; in potassium ions rich conditions, compounds 2,3 and 4 can all reversibly interconvert the original mixed-hybrid type G-quadruplex structure of d(TTAGGG)4 to the antiparallel form upon reversible irradiation by UV/Vis photoillumination; in sodium ions rich conditions, compound 3 can gradually reversibly transform the former antiparallel type of G-quadruplex to parallel form with a transition state of mixed-type structure upon reversible irradiation by UV/Vis photoillumination. However, the design needs to be further researched in the mimic molecular crowding conditions.