Radiolabeling peptides in fewer steps

A study published in Nature Communications on 12 June 2026 describes a method for installing carbon-14 or tritium radiolabels directly onto peptide molecules while they are still attached to the solid support used in synthesis^[1]. Developed by researchers at Aarhus University, AstraZeneca, and Sanofi, the technique converts an allylglycine residue into a radiolabeled lysine through hydroformylation and reductive amination. The team demonstrated it on peptides as complex as semaglutide analogs.

Why radiolabeled peptides matter in drug development

Before a peptide drug can reach patients, regulators expect data on how the molecule is absorbed, distributed, metabolized, and excreted (ADME). The standard way to track a drug through the body is to tag it with a radioactive isotope, typically carbon-14 or tritium, and then follow where the radioactivity ends up. These mass-balance studies are a routine part of clinical pharmacology programmes for small-molecule drugs^[1].

For peptides, however, radiolabeling has been expensive and technically difficult. The conventional approach is either to attach an external radioactive tag to the molecule, which changes its structure and may alter its behavior, or to rebuild the entire peptide from scratch using radiolabeled amino acid building blocks. Both routes are slow, costly, and limit the number of radiolabeled studies that pharmaceutical companies can run during development. As the pipeline of incretin-class drugs expands, with molecules like tirzepatide and retatrutide joining semaglutide in late-stage trials, the bottleneck becomes more pressing.

How the new method works

The researchers built their platform around a two-step chemical sequence performed on peptides still anchored to the solid-phase synthesis resin. First, they incorporated allylglycine, a non-natural amino acid with a short carbon-carbon double bond side chain, at a position in the peptide sequence where a lysine residue is wanted. Then they performed a hydroformylation reaction using either carbon-14-labeled carbon monoxide (from a solid precursor) or tritium gas, converting the allylglycine side chain into an allysine aldehyde carrying the radioactive label^[1].

In the second step, a reductive amination converts the aldehyde into an amine, producing a lysine residue. When the peptide is cleaved from the solid support, the result is a peptide containing a radiolabeled lysine at a defined position. Because the hydroformylation setup can use either carbon-14 carbon monoxide or tritium gas, the same workflow produces either isotope label^[1].

What the researchers demonstrated

The authors report that the optimized workflow tolerates diverse peptide sequences. Their most demanding test case was semaglutide analogs, the GLP-1 receptor agonist marketed as Ozempic and Wegovy. Semaglutide is a 31-amino-acid peptide with a fatty acid modification and several non-natural amino acid substitutions, making it one of the more structurally complex peptides in clinical use. Successfully labeling analogs of this molecule suggests the method can handle most therapeutic peptides currently in development or on the market^[1].

The work came from a collaboration between Troels Skrydstrup's group at Aarhus University, which specializes in carbon monoxide chemistry and isotope labeling^[2], and medicinal chemistry teams at AstraZeneca and Sanofi. That combination of academic catalysis expertise and pharmaceutical industry application is typical of how radiolabeling methods reach drug development pipelines.

What this does not tell us

The study is a methods paper, not a drug development programme. It demonstrates that the chemistry works on complex peptide sequences, but it does not report full radiochemical yields for every substrate or provide data on the metabolic behavior of the labeled peptides in living systems. Those experiments would come later, when a pharmaceutical company applies the technique to a specific drug candidate entering clinical pharmacology studies.

The method also does not change anything about the peptide drugs themselves. Radiolabeling is a tool for studying how a drug moves through the body; it does not alter the drug's therapeutic effects or safety profile. Patients taking semaglutide or other peptide medications are not affected by advances in radiolabeling chemistry.

Why it matters for the peptide field

The peptide therapeutics market is growing rapidly, driven by GLP-1 receptor agonists and related incretin-class drugs. As more peptide drug candidates enter clinical development, the demand for radiolabeled versions of these molecules will increase. A method that can install isotope labels late in the synthesis, without rebuilding the entire peptide, could reduce both the cost and the timeline for generating the ADME data that regulators require^[1].

If you are taking or considering a peptide-based medication, this research does not change your treatment. Consult your healthcare provider about any questions regarding your medication.