Cysteinyl Radicals: A Versatile Chemistry Tool for Peptide Synthesis and Natural Biology | Research

The takeaway

Review of cysteinyl radical chemistry covering their roles in both chemical peptide synthesis (enabling new stapling and modification strategies) and natural biological processes including enzyme catalysis.

Radical new chemistry
Cysteinyl radicals enable peptide modifications impossible with conventional chemistry — expanding what's achievable in peptide drug design

What the researchers found

Cysteinyl radicals enable novel peptide synthesis strategies including stapling and selective modifications, while also playing important roles in natural enzyme catalysis and redox biology.

Why it matters

New chemical reactions using cysteinyl radicals expand the toolkit for making peptide drugs, enabling modifications that are impossible with conventional chemistry.

The numbers in context

Synthetic uses: lipidation, glycosylation, labeling, macrocyclization, stapling, desulfurization; biological: DNA repair, metabolism, photochemistry

How the study worked

Narrative review of cysteinyl radical chemistry in both synthetic and biological contexts.

Who was studied

N/A (chemistry and biology review)

What this study cannot tell us

Chemistry review. Radical reactions can be challenging to control. Scale-up for pharmaceutical manufacturing needs development. Selectivity may vary between peptide substrates.

How to read the evidence

Not applicable (chemistry review).

When this study was published

Published 2021. Radical peptide chemistry continues advancing.

The bigger picture

Radical chemistry is expanding the boundaries of what can be done with peptide molecules, enabling modifications that create more stable, active, and selective peptide drugs.

Questions still open

Can radical-based peptide modifications be scaled for drug manufacturing?
Which peptide drug targets benefit most from radical chemistry approaches?
Do radical-modified peptides show improved stability or activity?

Common questions

What are cysteinyl radicals?

Cysteine amino acids contain sulfur, which can form highly reactive radical species under certain conditions. These radicals enable unique chemical reactions that modify peptides in ways conventional chemistry cannot — creating new bonds, structures, and properties.

How does this help drug development?

Radical chemistry opens new ways to make peptide drugs more stable, selective, and potent. For example, cysteinyl radicals can create new types of staples that lock peptides into their active shape, or attach drug molecules at positions conventional chemistry can't reach.

Read the original research

Cysteinyl radicals in chemical synthesis and in nature.

Chemical Society reviews, 50(19), 10857-10894

View on PubMed ↗Publisher’s paper ↗

Citation

McLean, Joshua T; Benny, Alby; Nolan, Mark D; Swinand, Glenna; Scanlan, Eoin M. (2021). Cysteinyl radicals in chemical synthesis and in nature.. Chemical Society reviews, 50(19), 10857-10894. https://doi.org/10.1039/d1cs00254f