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Updated: May 8, 2026

Functional Surface-immobilization of Genes Using Multistep Strand Displacement Lithography
Published on: October 25, 2018
Site-specifically arraying small molecules or proteins on DNA using an expanded genetic alphabet.
Zhengtao Li1, Thomas Lavergne1, Denis A Malyshev1
1Department of Chemistry and Dr. P. Ordoukhanian Center for Protein and Nucleic Acid Research The Scripps Research Institute 10550 North Torrey Pines Road La Jolla, CA 92037.
Researchers developed novel unnatural DNA base pairs for site-specific labeling. These synthetic DNA base pairs enable the attachment of tags and proteins, advancing applications in nanomaterials and biotechnology.
Area of Science:
- Synthetic Biology
- Biochemistry
- Molecular Biology
Background:
- Unnatural DNA base pairs (UBPs) offer expanded functionality beyond natural nucleobases.
- Site-specific modification of DNA is crucial for various biotechnological applications.
Purpose of the Study:
- To develop and characterize novel replicable unnatural DNA base pairs for site-specific DNA labeling.
- To explore the synthesis and polymerase-mediated replication of UBP derivatives.
- To demonstrate the utility of UBPs for attaching tags and proteins to DNA.
Main Methods:
- Synthesis of d5SICS, dMMO2, dDMO, and dNaM derivatives with propynyl groups.
- Polymerase-mediated replication of DNA containing UBPs.
- Site-specific modification of amplified DNA using Click chemistry.
- Attachment of biotin and proteins to DNA via UBPs.
- Visualization of protein-DNA conjugates using atomic force microscopy.
Main Results:
- Developed replicable unnatural DNA base pairs using d5SICS, dMMO2, dDMO, and dNaM scaffolds.
- Identified optimal linker attachment sites and types for UBP derivatives.
- Successfully site-selectively attached biotin and proteins to amplified DNA.
- Demonstrated the ability to couple one or two proteins to DNA using specific UBP constructs.
Conclusions:
- Novel unnatural DNA base pairs can be replicated and site-specifically functionalized.
- These UBPs facilitate the attachment of diverse molecules, including proteins, to DNA.
- This technology holds promise for applications in SELEX and the development of DNA-based nanomaterials.
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