Dual reactivity disulfide bridging reagents; enabling new approaches to antibody fragment bioconjugation.

ABSTRACT: Disulfide bridging, also known as disulfide stapling, is a powerful strategy for the construction of site-selective protein bioconjugates. Here we describe the first examples of a new class of such reagents, containing a 'stable-labile' design. These dual-reactive reagents are designed to form a stable bond to one cysteine and a labile bond to the second; resulting in a robust attachment to the protein with one end of the bridge, whilst the other end serves as a reactive handle for subsequent bioconjugation. By incorporating thioesters into these bridges, we demonstrate that they are primed for native chemical ligation (NCL) with N-terminal cysteines; offering an alternative to the requirement for C-terminal thioesters for use in such ligations. Alternatively, the use of hydrazine as the l

SUBMITTER: Chrzastek A 

PROVIDER: S-EPMC9555722 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature