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Ruthenium photolinkers for manipulating molecular structure and function in materials science and biology


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.



From Griepenburg et al, 2015.  RuBEP photolinker conjugated with 25mer bis-azido morpholino formed caged antisense morpholino; subsequent 450 nm irradiation restored biologically active morpholino.



  • 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

Stage of Development:   

In vitro proof-of-concept and in vivo regulation of zebrafish gene expression 


Intellectual Property: 

PCT pending (WO2016022526 A1)


Reference Media: 

Griepenburg J.C. et al.  Chem. Sci., 2015, 6, p. 2342-2346.


Desired Partnerships: 

  1. License
  2. Co-development

Docket # 15-7215



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Patent Information:
For Information, Contact:
Cortney Cavanaugh
Licensing Officer, SEAS/SAS Licensing Group
University of Pennsylvania
Ivan Dmochowski