1,4 - dihidropiridīna atvasinājumu (AV-153-sāļu) mijiedarbības izpēte pret c-Myc antiparalēlo kvadrupleksu, izmantojot UV/redzamo spektroskopiju
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Latvijas Universitāte
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lav
Abstract
Pedējos gados ievērojami pastiprinājusies uzmanība pret DNS guanīna kvadrupleksiem un to lomu onkoģenēzē. c-Myc proto-onkogēna pastiprināta ekspresija ir saistīta ar dažādiem cilvēka audzējiem, ka arī ar slikto prognozi. Līdz ar to DNS guanīna kvadrupleksu veidošana un stabilizācija C-myc promoter reģionos ir kritiska c-Myc trankripcijas inhibēšanai, tāpēc pēdējos gados aktīvi tiek meklēti savienojumi, kuri var stabilizēt G-kvadrupleksu struktūras un inhibēt c-Myc gēna ekspresiju. Šī pētījuma darba mērķis bija izpētīt 1,4-dihidropiridīna atvasinājumu (AV-153 sāļu un to analoga AV-154-Na sāls) spēju mijiedarboties ar antiparalēlo c-myc kvadrupleksu, kā arī spēju mijiedarboties ar vienpavadiena formu, izmantojot UV/ redz. spektroskopiskas titrēsanas metodi. Tika atklāts ka dažiem AV-153 sāļiem pastāv spēja mijiedarboties ar abām pētījumam izvēlētajām formām. Visaugstāko afinitāti pret c-myc kvadrupleksu parādija AV-154-Na sāls ka arī AV-153 K un Li sāļi.
In recent years, the focus on DNA guanine quadruplexes and their role in oncogenesis has increased significantly. Overexpression of c-Myc proto-oncogene is associated with a variety of human tumors and poor prognosis. Thus, the formation and stabilization of DNA guanine quadruplexes in c-Myc promoter regions is critical for inhibiting c-Myc transcription, therefore, the development of compounds which can stabilize G-quadruplex structures and inhibit c-Myc gene expression have been actively investigated. The aim of this study was to investigate the ability of 1,4-dihydropyridine derivatives (AV-153 salts and their analog AV-154-Na salt) to interact with the antiparallel c-Myc quadruplex, as well as the ability to interact with the single-stranded form using UV/VIS spectroscopic titration method. It was found that some salts of AV-153 have the ability to interact with both forms selected for the study. The highest affinity for the c-Myc quadruplex was shown by the K and Li salts and the AV-154-Na salt.
In recent years, the focus on DNA guanine quadruplexes and their role in oncogenesis has increased significantly. Overexpression of c-Myc proto-oncogene is associated with a variety of human tumors and poor prognosis. Thus, the formation and stabilization of DNA guanine quadruplexes in c-Myc promoter regions is critical for inhibiting c-Myc transcription, therefore, the development of compounds which can stabilize G-quadruplex structures and inhibit c-Myc gene expression have been actively investigated. The aim of this study was to investigate the ability of 1,4-dihydropyridine derivatives (AV-153 salts and their analog AV-154-Na salt) to interact with the antiparallel c-Myc quadruplex, as well as the ability to interact with the single-stranded form using UV/VIS spectroscopic titration method. It was found that some salts of AV-153 have the ability to interact with both forms selected for the study. The highest affinity for the c-Myc quadruplex was shown by the K and Li salts and the AV-154-Na salt.