Insights into the binding mode of AS1411 aptamer to nucleolin

Abstract

AS1411 aptamer can function as a recognition probe to detect the cell surface nucleolin overexpressed in cancer cells, however, little is known about their binding process. This study proposed a feasible binding mode for the first time and provided atomic-level descriptions for the high affinity and specific binding of AS1411. The binding pose predicted by docking was screened using knowledge-based criteria, and a microsecond molecular dynamics (MD) simulation showed the stable existence of the predicted structure in the solution. Structural analysis shows that the unique capping of the 5′ end of AS1411 provides the specific binding with RBD1, and the interactions of hydrogen bond, salt bridge, and water-mediated network between AS1411 and RBD1,2 stabilize the binding. The calculation of per-residue decomposition emphasizes the dominant contribution of van der Waals energy and critical residues are screened. Our study provides the molecular basis of this specific binding and can guide rational AS1411-based aptamers design. Further insights require tight collaborations between the experiments and in silico studies.

Arrays of graphene-quantum dots-supported DNA oligonucleotides as self-indicating porphyrin carriers

“…Therefore, the next step (Scheme 1, step 2) involved the coupling of the GQDs-B/AG-ED with the different 5’-Phos-DNA oligonucleotide sequences (G4-1 to non-G4, summarized in Table 1). The DNA sequences were chosen to allow the formation of different polymorphic arrays: (i) G4-1 is a sequence that corresponds to an adenine-extended version of the AS1411 aptamer, an aptamer that is able to form unimolecular G4s with proven affinity for proteins expressed in tumoral cells; 55 (ii) G4-2 mimics the G-rich human telomeric motif and is able to fold into unimolecular G4, (iii) G4-3 presents two consecutive repetitions of G-rich segments and, therefore, two chains must be involved in the formation of bimolecular intermolecular G4 structures and, at last, (iv) non-G4 is a non-G-rich sequence and thus it cannot fold as G4.…”

Engineered aptamers for molecular imaging

“…The interactions between aptamers and ligands involve several effects, such as electrostatic forces, 58 hydrogen bonds, 59 hydrophobic effect, 60 π–π stacking 61 and van der Waals force. 62,63 In addition, the structure of the aptamer can change with temperature and pH. 64 Considering that aptamers are susceptible to degradation and removal in the physiological environment, researchers have developed various nucleic acid modification methods to improve the stability of aptamers in molecular imaging applications.…”

Synergistic Viro-chemoimmunotherapy in Breast Cancer Enabled by Bioengineered Immunostimulatory Exosomes and Dual-Targeted Coxsackievirus B3

“…25 The AS1411 aptamer is a nonimmunogenic and thermally stable DNA aptamer, comprising 26 guanine-rich nucleotides with a quadruplex structure. 26 The AS1411 aptamer can serve not only as a detection tool to identify nucleolin, a cell surface protein that is overexpressed in many cancer cells, 27 but also as a targeting agent on the surface of various drug delivery systems. 28,29 In the current study, we aimed to improve tumor delivery and therapeutic efficacy by encapsulating oncolytic CVB3 within Exos, through modifying Exos with the AS1411 aptamer, and by combining CVB3 with a chemotherapy drug.…”