Synthesis of carbon-14-labelled peptides

Area of Science:

• Radiopharmaceutical chemistry
• Analytical chemistry
• Clinical pharmacology

Background:

• Carbon-14 (¹⁴ C)-labelled compounds are essential for pharmacokinetic studies in drug development.
• Mass balance and micro-dosing clinical trials require labelled active pharmaceutical ingredients (APIs) and investigational medicinal products (IMPs).
• ¹⁴ C-labelled peptides are increasingly important for specific therapeutic areas.

Purpose of the Study:

• To describe the synthesis and analysis of ¹⁴ C-labelled peptides for clinical trials.
• To highlight the utility of accelerated mass spectrometry (AMS) for analysing ¹⁴ C-peptides.
• To outline the application of solid-phase peptide synthesis (SPPS) in preparing these critical compounds.

Main Methods:

• ¹⁴ C-labelled peptides are synthesized using solid-phase peptide synthesis (SPPS).
• Custom-made glassware is employed for critical coupling steps during SPPS.
• Purified ¹⁴ C-peptides undergo further modifications as needed.

Main Results:

• Successful synthesis of ¹⁴ C-labelled peptides is achievable via SPPS.
• AMS provides a sensitive method for the analysis of these labelled peptides.
• The methodology allows for subsequent modifications of the synthesized peptides.

Conclusions:

• SPPS is a viable method for producing ¹⁴ C-labelled peptides for clinical trials.
• ¹⁴ C-labelled peptides are crucial for mass balance and micro-dosing studies.
• The described approach facilitates the development of radiolabelled peptide-based therapeutics.