Choosing an effective protein bioconjugation strategy

Nicholas Stephanopoulos, Matthew B. Francis

Research output: Contribution to journalReview articlepeer-review

478 Scopus citations


The collection of chemical techniques that can be used to attach synthetic groups to proteins has expanded substantially in recent years. Each of these approaches allows new protein targets to be addressed, leading to advances in biological understanding, new protein-drug conjugates, targeted medical imaging agents and hybrid materials with complex functions. The protein modification reactions in current use vary widely in their inherent site selectivity, overall yields and functional group compatibility. Some are more amenable to large-scale bioconjugate production, and a number of techniques can be used to label a single protein in a complex biological mixture. This review examines the way in which experimental circumstances influence one's selection of an appropriate protein modification strategy. It also provides a simple decision tree that can narrow down the possibilities in many instances. The review concludes with example studies that examine how this decision process has been applied in different contexts.

Original languageEnglish (US)
Pages (from-to)876-884
Number of pages9
JournalNature Chemical Biology
Issue number12
StatePublished - Dec 2011
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


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