Perspective | Published:

Targeting the N terminus for site-selective protein modification

Nature Chemical Biology volume 13, pages 697705 (2017) | Download Citation

Abstract

The formation of well-defined protein bioconjugates is critical for many studies and technologies in chemical biology. Tried-and-true methods for accomplishing this typically involve the targeting of cysteine residues, but the rapid growth of contemporary bioconjugate applications has required an expanded repertoire of modification techniques. One very powerful set of strategies involves the modification of proteins at their N termini, as these positions are typically solvent exposed and provide chemically distinct sites for many protein targets. Several chemical techniques can be used to modify N-terminal amino acids directly or convert them into unique functional groups for further ligations. A growing number of N-terminus-specific enzymatic ligation strategies have provided additional possibilities. This Perspective provides an overview of N-terminal modification techniques and the chemical rationale governing each. Examples of specific N-terminal protein conjugates are provided, along with their uses in a number of diverse biological applications.

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Acknowledgements

This work was supported by the National Science Foundation (CHE-1413666). C.B.R. was supported by the Villum Kann Rasmussen Foundation. The authors thank J.I. MacDonald for helpful comments and suggestions for this manuscript.

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Affiliations

  1. Department of Chemistry, University of California, Berkeley, Berkeley, California, USA.

    • Christian B Rosen
    •  & Matthew B Francis
  2. Materials Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California, USA..

    • Matthew B Francis

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The authors declare no competing financial interests.

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Correspondence to Matthew B Francis.

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https://doi.org/10.1038/nchembio.2416

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