Transient Transcription Machineries Modulate Dynamic Functions of G-Quadruplexes: Temporal Regulation of Biocatalytic Circuits, Gene Replication and Transcription.

Angew Chem Int Ed Engl

The Institute of Chemistry, The Center for Nanoscience and Nanotechnology, The Hebrew University of Jerusalem, Jerusalem, 91904, Israel.

Published: August 2023

Native G-quadruplex-regulated temporal biocatalytic circuits, gene polymerization, and transcription processes are emulated by biomimetic, synthetically engineered transcription machineries coupled to reconfigurable G-quadruplex nanostructures. These are addressed by the following example: (i) A reaction module demonstrates the fuel-triggered transcription machinery-guided transient synthesis of G-quadruplex nanostructures. (ii) A dynamically triggered and modulated transcription machinery that guides the temporal separation and reassembly of the anti-thrombin G-quadruplex aptamer/thrombin complex is introduced, and the transient thrombin-catalyzed coagulation of fibrinogen is demonstrated. (iii) A dynamically fueled transient transcription machinery for the temporal activation of G-quadruplex-topologically blocked gene polymerization circuits is introduced. (iv) Transcription circuits revealing G-quadruplex-promoted or G-quadruplex-inhibited cascaded transcription machineries are presented. Beyond advancing the rapidly developing field of dynamically modulated G-quadruplex DNA nanostructures, the systems introduce potential therapeutic applications.

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Source
http://dx.doi.org/10.1002/anie.202307898DOI Listing

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