Controlling the G‑Quadruplex Topology: Toward the Formation of a Lipid Thrombin Binding Aptamer Prodrug

Important efforts have been devoted toward the development of modified oligonucleotides capable of controlling the secondary structures of the G-quadruplex (G4). Herein, we introduce a photocleavable, lipidated construct of the well-known Thrombin Binding Aptamer (TBA) whose conformation can be dual...

Full description

Saved in:
Bibliographic Details
Published in:Bioconjugate chemistry 2023-07, Vol.34 (7), p.1198-1204
Main Authors: Vialet, Brune, Bansode, Nitin D., Gissot, Arnaud, Barthélémy, Philippe
Format: Article
Language:English
Subjects:
Aptamers
Aptamers, Nucleotide - chemistry
Aqueous solutions
Binding
Biochemistry, Molecular Biology
Biophysics
Chemical Sciences
Conformation
G-Quadruplexes
Ionic strength
Irradiation
Life Sciences
Light irradiation
Lipids
Medicinal Chemistry
Oligonucleotides
Pharmacodynamics
Prodrugs
Prodrugs - pharmacology
Radiation
Switches
Thrombin
Thrombin - chemistry
Topology
Citations: Items that this one cites
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Important efforts have been devoted toward the development of modified oligonucleotides capable of controlling the secondary structures of the G-quadruplex (G4). Herein, we introduce a photocleavable, lipidated construct of the well-known Thrombin Binding Aptamer (TBA) whose conformation can be dual-controlled by light and/or the ionic strength of the aqueous solution. This novel lipid-modified TBA oligonucleotide spontaneously self-assembles and switches from the conventional antiparallel aptameric fold at low ionic strength to the parallel, inactive conformation of the TBA oligonucleotide strands under physiologically relevant conditions. The latter parallel conformation can be readily and chemoselectively switched back to the antiparallel native aptamer conformation upon light irradiation. Our lipidated construct constitutes an original prodrug of the original TBA with properties that are prone to improving the pharmacodynamic profile of the unmodified TBA.
ISSN:1043-1802
1520-4812
DOI:10.1021/acs.bioconjchem.3c00170