Locking up the AS1411 Aptamer with a Flanking Duplex: Towards an Improved Nucleolin-Targeting. Miranda, A., Santos, T., Largy, E., & Cruz, C. Pharmaceuticals, 14(2):121, February, 2021. Paper doi abstract bibtex We have designed AS1411-N6, a derivative of the nucleolin (NCL)-binding aptamer AS1411, by adding six nucleotides to the 5′-end that are complementary to nucleotides at the 3′-end forcing it into a stem-loop structure. We evaluated by several biophysical techniques if AS1411-N6 can adopt one or more conformations, one of which allows NCL binding. We found a decrease of polymorphism of G-quadruplex (G4)-forming sequences comparing to AS1411 and the G4 formation in presence of K+ promotes the duplex folding. We also studied the binding properties of ligands TMPyP4, PhenDC3, PDS, 360A, and BRACO-19 in terms of stability, binding, topology maintenance of AS1411-N6, and NCL recognition. The melting experiments revealed promising stabilizer effects of PhenDC3, 360A, and TMPyP4, and the affinity calculations showed that 360A is the most prominent affinity ligand for AS1411-N6 and AS1411. The affinity determined between AS1411-N6 and NCL denoting a strong interaction and complex formation was assessed by PAGE in which the electrophoretic profile of AS1411-N6 showed bands of the dimeric form in the presence of the ligands and NCL.
@article{miranda_locking_2021,
title = {Locking up the {AS1411} {Aptamer} with a {Flanking} {Duplex}: {Towards} an {Improved} {Nucleolin}-{Targeting}},
volume = {14},
copyright = {All rights reserved},
issn = {1424-8247},
shorttitle = {Locking up the {AS1411} {Aptamer} with a {Flanking} {Duplex}},
url = {https://www.mdpi.com/1424-8247/14/2/121},
doi = {10.3390/ph14020121},
abstract = {We have designed AS1411-N6, a derivative of the nucleolin (NCL)-binding aptamer AS1411, by adding six nucleotides to the 5′-end that are complementary to nucleotides at the 3′-end forcing it into a stem-loop structure. We evaluated by several biophysical techniques if AS1411-N6 can adopt one or more conformations, one of which allows NCL binding. We found a decrease of polymorphism of G-quadruplex (G4)-forming sequences comparing to AS1411 and the G4 formation in presence of K+ promotes the duplex folding. We also studied the binding properties of ligands TMPyP4, PhenDC3, PDS, 360A, and BRACO-19 in terms of stability, binding, topology maintenance of AS1411-N6, and NCL recognition. The melting experiments revealed promising stabilizer effects of PhenDC3, 360A, and TMPyP4, and the affinity calculations showed that 360A is the most prominent affinity ligand for AS1411-N6 and AS1411. The affinity determined between AS1411-N6 and NCL denoting a strong interaction and complex formation was assessed by PAGE in which the electrophoretic profile of AS1411-N6 showed bands of the dimeric form in the presence of the ligands and NCL.},
language = {en},
number = {2},
urldate = {2024-01-05},
journal = {Pharmaceuticals},
author = {Miranda, André and Santos, Tiago and Largy, Eric and Cruz, Carla},
month = feb,
year = {2021},
keywords = {AS1411 derivative, DNA aptamers, G-quadruplex, biophysical characterization},
pages = {121},
}
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