Chromophore engineering of isoquinoline aldehydes generates TICT-based fluorogenic dyes for in situ labeling of diverse (bio)molecules with large Stokes shifts compatible with cell imaging.

Abstract. Site-specifically attaching biorthogonal handles to proteins is an essential tool for chemical biology research and diverse applications, includi

A cysteine-selective bioconjugation using aromatic cyclopropenium cations is reported. The reaction proceeds rapidly under aqueous conditions, enabling site-selective installation of tetrasubstituted...

To date, a variety of covalent cysteine-reactive chemical probes have been reported. The most common ones include maleimide for bioconjugation and iodoacetamide alkyne (IAA) for chemoproteomics analys...

The (bio)conjugation of polymers onto proteins enhances their pharmacokinetics and stability, most commonly using PEG (polyethylene glycol), but there is a need for alternatives. Poly(vinyl alcohol), ...

This student-authored review highlights notable advances in synthetically enabled chemical biology from 2025, spanning bioconjugation and bioorthogonal chemistry, visualization and sensing, precision...

Affinity-driven reactions have allowed chemists to perform site-selective modifications of native proteins. By combining the high cysteine chemoselectivity of hypervalent iodine-based ethynylbenziodox...

Nature Chemistry, Published online: 28 August 2026; doi:10.1038/s41557-026-02227-1Spatiotemporal control over bioorthogonal reactions remains challenging. Now cyclopropanol has been shown to act as a functional moity that is inert under physiological conditions but can be selectively activated by mild electrochemical stimuli to preferentially modify acidic amino acids, such as glutamate and aspartate, within hydrophobic regions of proteins.

We introduce aryl thiols as nucleophiles for site-specific protein and antibody bioconjugation, which allows the orthogonal labeling of native cysteines for double modification strategies. In a high-y...

In this issue of Chem, Zhang and colleagues report a biomimetic polarity-reversal strategy for lysine-targeted bioconjugation. Leveraging ortho-quinone as an oxidant, this approach directly converts the ε-amino group of lysine to an aldehyde moiety under physiological conditions, enabling site-specific modification of peptides and proteins with unprecedented biocompatibility, chemoselectivity, and versatility.

Chemoselective dual functionalization of proteins is an invaluable tool to introduce two distinct payloads to proteins. Here, the authors present N-alkylpyridinium reagents as soft electrophiles for c...

The sulfo-click reaction, which relies on the chemoselective coupling of sulfonyl azides with thioacids to yield N-acylsulfonamides, has emerged as a powerful and versatile transformation in…

Triphenylphosphonium ylides (Wittig reagents) that selectively react with sulfenic acids—a pivotal post-translational cysteine modification in redox biology—are developed. This bioconjugation method e...