Site-Specific and Trigger-Activated Modification of Proteins by Means of Catalytic Hemin/G-quadruplex (hGQ) DNAzyme Nanostructures

22 July 2020, Version 1
This content is a preprint and has not undergone peer review at the time of posting.


Synthetic DNA that forms various G-quadruplex nanostructures, in combination with hemin, N-methyl luminol derivatives, and H2O2 can site-specifically modify proteins (i.e. evidence is provided for lysozyme and human alpha-thrombin). The catalytic modification is completed in 15-30 mins, and the site-specificity is influenced by the G-quadruplex topology (a total of 22 G-quadruplex forming sequences was tested). We also show that the heavy chain of the therapeutic antibody trastuzumab is modified, which facilitates the preparation of antibody-drug conjugates. Furthermore, a trigger can be programmed into this synthetic DNA so that the protein modification chemistry is made dependent on an external trigger.

Techniques used: HPLC, SDS-PAGE, LC-MS/MS, NMR.


bioconjugation chemistry
enzyme mimic
chemical biology
DNA nanotechnology

Supplementary materials

Keijzer SI


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