New paradigm for caging and photoreleasing polymeric systems with visible light responsive ruthenium photolinkers.

Photochemical methods can manipulate and regulate molecular structure, function, and localization. Site-specifically incorporating a photolabile moiety within an oligonucleotide has remained a synthetic challenge. Moreover, methods for achieving multiplexing of caged molecules with multiple caging chromophores are not widely available, with antisense morpholinos, used to block mRNA translation in model organisms, as the primary focus of caged oligo development.

The Dmochowski Lab has developed the first visible light responsive ruthenium-based photolinker that can circularize biomolecules. More specifically, a Ru(bpy)2(3-ethynylpyridine)2 (RuBEP) compound has been created, where the ethynyl moieties are reacted with a bis-azido oligonucleotide and click chemistry. 

This concept can be readily expanded to cage peptides, lipids, or other polymers. The ruthenium photolinker can be blue- or red-shifted, and the bioconjugation chemistry can also be altered. 

The researchers have implemented the technology using RuBEP-caged circular morpholinos that targeted early development zebrafish genes, where uncaged morpholinos successfully achieved gene knockdown.

• Visible light excitation and activation of caged oligos
• Ruthenium photolinker amenable to caging oligos and large biomolecules
• Mild synthetic conditions

• Molecular caging to study amino acids, peptides, oligonucleotides, neurotransmitters, and other biologically relevant molecules
• Photochemical methods
• Gene regulation and expression
• Control structure and function of biopolymers, materials, biological systems