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From DNA to Protein

From DNA to Protein

The flow of genetic information in cells from DNA to mRNA to protein is described by the central dogma, which states that genes specify the sequence of mRNAs, which in turn specify the sequence of amino acids making up all proteins. The decoding of one molecule to another is performed by specific proteins and RNAs. Because the information stored in DNA is so central to cellular function, it makes intuitive sense that the cell would make mRNA copies of this information for protein synthesis...

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Related Experiment Video

Updated: Jun 18, 2026

Genetic Incorporation of Biosynthesized L-dihydroxyphenylalanine (DOPA) and Its Application to Protein Conjugation

Genetic Incorporation of Biosynthesized L-dihydroxyphenylalanine (DOPA) and Its Application to Protein Conjugation

Published on: August 24, 2018

Scalable Flow Synthesis of Genetically Encodable Tetrazine Amino Acids.

Yogesh M Gangarde¹, Erik C Carlson², Matthew A Cranswick²

¹Oregon State University, Department of Biochemistry and Biophysics, 2011 Agricultural and Life Sciences, Corvallis, OR 97331.

Organic Process Research & Development

|June 17, 2026

Summary

Researchers developed safer, scalable flow chemistry methods for tetrazine-bearing noncanonical amino acids (Tet-ncAAs). This sustainable approach supports applications in drug conjugates and bioconjugation, meeting growing industrial demand.

Keywords:

Tetrazine amino acids continuous flow synthesis genetic code expansion

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Last Updated: Jun 18, 2026

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Published on: August 24, 2018

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Published on: February 6, 2020

Area of Science:

Chemical Biology
Organic Synthesis
Bioconjugation Chemistry

Background:

Tetrazine-cyclooctene ligation is a rapid bioorthogonal reaction crucial for bioconjugation.
Genetic code expansion enables site-specific protein incorporation of tetrazine-bearing noncanonical amino acids (Tet-ncAAs).
Current Tet-ncAA synthesis methods are small-scale, hazardous, and difficult to scale.

Purpose of the Study:

To develop safer, scalable, and reproducible synthetic routes for Tet-ncAAs.
To establish environmentally friendly synthesis conditions for Tet-ncAAs.
To meet the increasing demand for Tet-ncAAs in various bioconjugation applications.

Main Methods:

Utilized hybrid batch-flow and continuous flow synthesis for Tet-ncAAs.
Employed aqueous hydrazine, 3-mercaptopropionic acid catalyst, and optimized temperature conditions.
Integrated a continuous oxidation protocol for tetrazine product formation.

Main Results:

Achieved multigram-scale synthesis of diverse Tet-ncAAs from commercial precursors.
Demonstrated improved process safety, scalability, and reproducibility compared to batch methods.
Established milder, safer, and environmentally friendly synthesis conditions.

Conclusions:

The developed flow chemistry platform provides a safer, scalable, and sustainable route to Tet-ncAAs.
This method supports the growing demand for Tet-ncAAs in antibody-drug conjugates, imaging, and targeted delivery.
The modular process is adaptable for synthesizing various Tet-ncAAs efficiently.