Опубликована: Янв. 1, 2024
Язык: Английский
Опубликована: Янв. 1, 2024
Язык: Английский
Applied Biological Chemistry, Год журнала: 2025, Номер 68(1)
Опубликована: Янв. 20, 2025
Язык: Английский
Процитировано
0Molecules, Год журнала: 2025, Номер 30(8), С. 1673 - 1673
Опубликована: Апрель 8, 2025
AS1411 is a G-quadruplex (G4) aptamer that binds tightly to nucleolin (NCL) on the cell surface and has shown strong anticancer effects. However, this highly polymorphic, presenting different types of G4s, which may hinder its preclinical application. Several modifications have been made decrease polymorphism aptamer. In work, we designed six derivatives by substituting guanine with thymine in central linker modifying number thymines either itself and/or at both ends sequence. The G4 formation, stability, NCL binding were evaluated several biophysical techniques computational studies. Overall, G4-forming sequences compared observed size exclusion chromatography (SEC) circular dichroism (CD) spectroscopy presence potassium salt. melting experiments reveal higher ability without sequence form G4, consistent G4H score predictions. Additionally, it possible conclude deletions T core increase G4. Moreover, bind high affinity (KD values 10−9 M range), particularly only linker. silico studies structural insights demonstrate interact NCL, establishing multiple interactions domains, thereby further supporting experimental findings. By using lung cancer line expression, evaluate internalization uptake derivatives, identifying derivative-lacking as ones highest cellular uptake.
Язык: Английский
Процитировано
0Опубликована: Янв. 1, 2024
Язык: Английский
Процитировано
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