Peptide‐Directed DNA‐Templated Protein Labelling for The Assembly of a Pseudo‐IgM

Nielsen, Thorbjørn B.; Thomsen, Rasmus P.; Mortensen, Michael; Kjems, Jørgen; Nielsen, Per F.; Nielsen, Thomas E.; Kodal, Anne Louise Bank; Cló, Emiliano; Gothelf, Kurt V.

doi:10.1002/ange.201903134

Cited by 8 publications

(1 citation statement)

References 31 publications

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“…The authors applied this peptide-directed DTPC for the preparation of monofunctionalized AOCs for their further assembly into a pseudo-IgM constructs. 164 Recently, affinity guided conjugation of proteins using aptamers as a guiding ONs has been described. 165 This method has been further used in Gothelf group for the AOC preparation.…”

Section: Bioconjugate Chemistrymentioning

confidence: 99%

Antibody–Oligonucleotide Conjugates as Therapeutic, Imaging, and Detection Agents

Dovgan

Koniev²,

Kolodych³

et al. 2019

Bioconjugate Chem.

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Antibody−oligonucleotide conjugates (AOCs) are a novel class of synthetic chimeric biomolecules that has been continually gaining traction in different fields of modern biotechnology. This is mainly due to the unique combination of the properties of their two constituents, exceptional targeting abilities and antibody biodistribution profiles, in addition to an extensive scope of oligonucleotide functional and structural roles. Combining these two classes of biomolecules in one chimeric construct has therefore become an important milestone in the development of numerous biotechnological applications, including imaging (DNA-PAINT), detection (PLA, PEA), and therapeutics (targeted siRNA/antisense delivery). Numerous synthetic approaches have been developed to access AOCs ranging from stochastic chemical bioconjugation to site-specific conjugation with reactive handles, introduced into antibody sequences through protein engineering. This Review gives a general overview of the current status of AOC applications with a specific emphasis on the synthetic methods used for their preparation. The reported synthetic techniques are discussed in terms of their practical aspects and limitations. The importance of the development of novel methods for the facile generation of AOCs possessing a defined constitution is highlighted as a priority in AOC research to ensure the advance of their new applications.

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Section: Bioconjugate Chemistrymentioning

confidence: 99%

Antibody–Oligonucleotide Conjugates as Therapeutic, Imaging, and Detection Agents

Dovgan

Koniev²,

Kolodych³

et al. 2019

Bioconjugate Chem.

View full text Add to dashboard Cite

show abstract

Identification of Histone deacetylase (HDAC)‐Associated Proteins with DNA‐Programmed Affinity Labeling

et al. 2020

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Histone deacetylase (HDAC) is a major class of deacetylation enzymes. Many HDACs exist in large protein complexes in cells and their functions strongly depend on the complex composition. The identification of HDAC‐associated proteins is highly important in understanding their molecular mechanisms. Although affinity probes have been developed to study HDACs, they were mostly targeting the direct binder HDAC, while other proteins in the complex remain underexplored. We report a DNA‐based affinity labeling method capable of presenting different probe configurations without the need for preparing multiple probes. Using one binding probe, 9 probe configurations were created to profile HDAC complexes. Notably, this method identified indirect HDAC binders that may be inaccessible to traditional affinity probes, and it also revealed new biological implications for HDAC‐associated proteins. This study provided a simple and broadly applicable method for characterizing protein‐protein interactions.

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1,3‐Diketone‐Modified Nucleotides and DNA for Cross‐Linking with Arginine‐Containing Peptides and Proteins

et al. 2021

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Linear or branched 1,3-diketone-linked thymidine 5'-O-mono-and triphosphate were synthesized through CuAAC click reaction of diketone-alkynes with 5-azidomethyl-dUMP or -dUTP. The triphosphates were good substrates for KOD XL DNA polymerase in primer extension synthesis of modified DNA. The nucleotide bearing linear 3,5dioxohexyl group (HDO) efficiently reacted with argininecontaining peptides to form stable pyrimidine-linked conjugates, whereas the branched 2-acetyl-3-oxo-butyl (PDO) group was not reactive. Reaction with Lys or a terminal amino group formed enamine adducts that were prone to hydrolysis. This reactive HDO modification in DNA was used for bioconjugations and cross-linking with Arg-containing peptides or proteins (e.g. histones).

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Peptide‐Directed DNA‐Templated Protein Labelling for The Assembly of a Pseudo‐IgM

Cited by 8 publications

References 31 publications

Antibody–Oligonucleotide Conjugates as Therapeutic, Imaging, and Detection Agents

Antibody–Oligonucleotide Conjugates as Therapeutic, Imaging, and Detection Agents

Identification of Histone deacetylase (HDAC)‐Associated Proteins with DNA‐Programmed Affinity Labeling

1,3‐Diketone‐Modified Nucleotides and DNA for Cross‐Linking with Arginine‐Containing Peptides and Proteins

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