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Updated: Feb 6, 2026

An Inexpensive Adaptation of a Commercial Microwave Reactor for Solid Phase Peptide Synthesis
Published on: November 22, 2024
Novel and Efficient Method for Solid Phase Synthesis of Urea-Containing Peptides Targeting Prostate Specific Membrane
Mona Mosayebnia1,2, Sedigheh Rezaeianpour1,3, Pedram Rikhtechi4
1M.M and S.R. contributed equally to this work.
Abstract:
The basic chemical structure of most prostate specific membrane antigen (PSMA) inhibitors which are now in pre-clinical and clinical studies is Glu-Ureido-based peptides. Synthesis of urea-based PSMA inhibitors includes two steps: 1- isocyanate intermediate formation and 2- urea bond formation. In current methods, isocyanate is formed in liquid phase and then reacts with amine existing in liquid phase or bound to solid phase for urea bond formation. In this study, we developed a new facile method for formation of both isocyanate and urea on solid phase under standard peptide coupling conditions. The solid phase-bound isocyanate served as intermediate to form urea bond. To monitor reaction progress qualitative test (Kaiser Test) and On-Bead FT-IR spectroscopy were used. The structure of Glutamate-Urea-Lysine (EUK) was confirmed using LC-Mass and 1H-NMR. This novel method successfully was applied to synthesize of another urea-based peptide containing a sequence of Glu-Urea-Lys (OMe)-GABA-Tyr-Tyr-GABA and the bifunctional linker hydrazinonicotinamide (HYNIC) as well.
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