Dynamic Expression of DNA Complexation with Self-assembled Biomolecular Clusters

Area of Science:

• Supramolecular Chemistry
• Chemical Biology
• Molecular Recognition

Background:

• Dynamic covalent chemistry (DCC) offers reversible bond formation for adaptive molecular systems.
• Multivalent interactions are crucial for specific biomolecular recognition, including DNA binding.
• In situ generation of complex structures via self-assembly is a key challenge in molecular engineering.

Purpose of the Study:

• To develop a DCC strategy for constructing multivalent clusters capable of DNA recognition.
• To investigate the in situ formation and DNA-binding properties of these self-assembled clusters.
• To explore the potential for template-directed assembly and effector-controlled DNA release.

Main Methods:

• Utilized chemoselective ligations for programmed self-assembly of biomolecular clusters.
• Employed fluorescence displacement assays, gel electrophoresis, and isothermal titration calorimetry to study DNA complexation.
• Investigated reversibility of ligation and component exchange for template effects and DNA release.

Main Results:

• Successfully generated cationic multivalent clusters using a DCC approach.
• Demonstrated effective DNA complexation by the clusters through multivalent interactions.
• Observed template effects where DNA directed the selection of more active DNA-binding clusters.
• Showcased effector-induced DNA release via component exchange reactions.

Conclusions:

• The DCC strategy enables the in situ generation of functional multivalent DNA-binding clusters.
• Reversible covalent chemistry facilitates template-directed self-assembly and controlled molecular recognition.
• This approach provides a platform for developing responsive DNA-binding agents and molecular systems.