Programmable site-selective labeling of oligonucleotides based on carbene catalysis

Area of Science:

• Chemical Biology
• Organic Chemistry
• Biotechnology

Background:

• Site-selective modification of oligonucleotides is crucial for biological research, biotechnology, and nanotechnology.
• Existing methods often lack the required precision for complex applications.

Purpose of the Study:

• To develop a chemo- and regioselective method for modifying oligonucleotides.
• To enable programmable and iterative introduction of functional handles onto DNA and RNA.

Main Methods:

• Utilized rhodium(I)-carbene catalysis for oligonucleotide modification.
• Performed extensive screening to identify a selective rhodium(I) catalyst.
• Engineered guanosine-bulge loops in duplex DNA to achieve regioselectivity.

Main Results:

• Identified a rhodium(I) catalyst with high chemoselectivity for base-unpaired guanosines.
• Achieved high regioselectivity among multiple guanosines within complex oligonucleotide structures.
• Demonstrated the utility of the method through DNA-protein cross-linking experiments in cell lysates.

Conclusions:

• Developed a programmable, site-selective oligonucleotide modification strategy using rhodium(I)-carbene catalysis.
• This approach offers precise control for introducing multiple functional groups, enabling advanced applications like DNA-protein cross-linking.