Symmetrical Branching Unit Alternative to Lysine-Core-Based Multiple Antigenic Peptides to Eradicate Isomeric Impurities.

The synthesis of multiple antigenic peptides (MAPs) remains challenging and is conventionally achieved by using Lys-based branching cores. However, the presence of two asymmetric amino groups in Lys results in the formation of multiple isomeric impurities. To address this limitation, a novel symmetrical branching unit based on s-triazine, Fmoc2-TBM-OH (TBM for triazine-bis-multipod, 1), was synthesized and applied in MAP synthesis. The TBM-based strategy enabled efficient four-copy MAP synthesis and produced a less complex impurity profile, demonstrating improved robustness, chromatographic behavior, and synthetic practicality.