Site-Selective Disulfide Modification of Proteins: Expanding Diversity beyond the Proteome

Chemistry. 2016 Nov 21;22(48):17112-17129. doi: 10.1002/chem.201602298. Epub 2016 Oct 25.

Abstract

The synthetic transformation of polypeptides with molecular accuracy holds great promise for providing functional and structural diversity beyond the proteome. Consequently, the last decade has seen an exponential growth of site-directed chemistry to install additional features into peptides and proteins even inside living cells. The disulfide rebridging strategy has emerged as a powerful tool for site-selective modifications since most proteins contain disulfide bonds. In this Review, we present the chemical design, advantages and limitations of the disulfide rebridging reagents, while summarizing their relevance for synthetic customization of functional protein bioconjugates, as well as the resultant impact and advancement for biomedical applications.

Keywords: bioactive hybrids; disulfide rebridging; drug delivery; multimodal proteins; site-selective protein modifications.

Publication types

  • Review

MeSH terms

  • Disulfides / chemistry*
  • Humans
  • Peptides / chemistry*
  • Proteins / chemistry*
  • Proteome

Substances

  • Disulfides
  • Peptides
  • Proteins
  • Proteome