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A noncanonical function of sortase enables site-specific conjugation of small molecules to lysine residues in proteins.

Publication ,  Journal Article
Bellucci, JJ; Bhattacharyya, J; Chilkoti, A
Published in: Angewandte Chemie (International ed. in English)
January 2015

We provide the first demonstration that isopeptide ligation, a noncanonical activity of the enzyme sortase A, can be used to modify recombinant proteins. This reaction was used in vitro to conjugate small molecules to a peptide, an engineered targeting protein, and a full-length monoclonal antibody with an exquisite level of control over the site of conjugation. Attachment to the protein substrate occurred exclusively through isopeptide bonds at a lysine ε-amino group within a specific amino acid sequence. This reaction allows more than one molecule to be site-specifically conjugated to a protein at internal sites, thereby overcoming significant limitations of the canonical native peptide ligation reaction catalyzed by sortase A. Our method provides a unique chemical ligation procedure that is orthogonal to existing methods, supplying a new method to site-specifically modify lysine residues that will be a valuable addition to the protein conjugation toolbox.

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Published In

Angewandte Chemie (International ed. in English)

DOI

EISSN

1521-3773

ISSN

1433-7851

Publication Date

January 2015

Volume

54

Issue

2

Start / End Page

441 / 445

Related Subject Headings

  • Proteins
  • Organic Chemistry
  • Lysine
  • Bacterial Proteins
  • 34 Chemical sciences
  • 03 Chemical Sciences
 

Citation

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Bellucci, J. J., Bhattacharyya, J., & Chilkoti, A. (2015). A noncanonical function of sortase enables site-specific conjugation of small molecules to lysine residues in proteins. Angewandte Chemie (International Ed. in English), 54(2), 441–445. https://doi.org/10.1002/anie.201408126
Bellucci, Joseph J., Jayanta Bhattacharyya, and Ashutosh Chilkoti. “A noncanonical function of sortase enables site-specific conjugation of small molecules to lysine residues in proteins.Angewandte Chemie (International Ed. in English) 54, no. 2 (January 2015): 441–45. https://doi.org/10.1002/anie.201408126.
Bellucci JJ, Bhattacharyya J, Chilkoti A. A noncanonical function of sortase enables site-specific conjugation of small molecules to lysine residues in proteins. Angewandte Chemie (International ed in English). 2015 Jan;54(2):441–5.
Bellucci, Joseph J., et al. “A noncanonical function of sortase enables site-specific conjugation of small molecules to lysine residues in proteins.Angewandte Chemie (International Ed. in English), vol. 54, no. 2, Jan. 2015, pp. 441–45. Epmc, doi:10.1002/anie.201408126.
Bellucci JJ, Bhattacharyya J, Chilkoti A. A noncanonical function of sortase enables site-specific conjugation of small molecules to lysine residues in proteins. Angewandte Chemie (International ed in English). 2015 Jan;54(2):441–445.
Journal cover image

Published In

Angewandte Chemie (International ed. in English)

DOI

EISSN

1521-3773

ISSN

1433-7851

Publication Date

January 2015

Volume

54

Issue

2

Start / End Page

441 / 445

Related Subject Headings

  • Proteins
  • Organic Chemistry
  • Lysine
  • Bacterial Proteins
  • 34 Chemical sciences
  • 03 Chemical Sciences