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Related Experiment Video

Updated: Jan 11, 2026

Aptamer-Based Target Detection Facilitated by a 3-Stage G-Quadruplex Isothermal Exponential Amplification Reaction

Aptamer-Based Target Detection Facilitated by a 3-Stage G-Quadruplex Isothermal Exponential Amplification Reaction

Published on: October 6, 2022

Loop topology enables programmable apoptosis in G-quadruplex aptamers.

Ahmed Shaarawy¹, Manal Fouad Ismail², Nagwa Ibrahim Shehata²

¹Biochemistry Department, Faculty of Pharmacy, Misr University for Science and Technology, 6th of October City, Giza 12566, Egypt.

Bioorganic Chemistry

|November 14, 2025

Summary

Loop architecture in G-quadruplex (G4) aptamers critically impacts biological activity. Tailoring loop topology offers a strategy for designing potent and selective nucleic acid therapeutics.

Keywords:

Apoptosis BCL2 Cell cycle arrest G-quadruplex aptamer Loop topology STAT3

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Last Updated: Jan 11, 2026

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Published on: May 12, 2023

Area of Science:

Biochemistry
Molecular Biology
Drug Discovery

Background:

G-quadruplex (G4) aptamers show therapeutic potential but their loop architecture's role is unclear.
Understanding G4 aptamer structure-activity relationships is key for developing nucleic acid therapeutics.

Purpose of the Study:

To compare the biological activity of two G4 aptamers with identical scaffolds but different loop topologies.
To investigate how loop configuration influences cytotoxicity, cell-cycle arrest, and gene expression.

Main Methods:

Designed and synthesized two unimolecular antiparallel G4 aptamers (2MFT and S172) with varying loop structures.
Assessed thermal stability, cellular potency, cytotoxicity, cell-cycle progression, and gene expression (apoptosis, STAT3, BCL2).
Evaluated cancer cell selectivity against normal fibroblasts.

Main Results:

Both aptamers showed similar thermal stability and low-nanomolar potency.
S172 induced faster, more pronounced cytotoxicity and G1-phase arrest with altered apoptotic gene expression.
2MFT demonstrated superior selectivity for cancer cells over normal fibroblasts, suggesting a wider therapeutic window.

Conclusions:

Loop topology is a critical determinant of G4 aptamer intracellular activity and apoptotic activation.
Findings support a threshold-based model for G4-mediated apoptosis.
Results provide a framework for topology-driven aptamer design for next-generation therapeutics.