Dmpic as an Orthogonal Protecting Group for Aspartic Acid Side Chains: Facilitating the Synthesis of Lactam-Cyclized Peptides

Orthogonal protection of the Asp side chain is critical in peptide synthesis. We introduce the 2-pyridyl isopropyl (Dmpic) group as a photolabile protecting group for the Asp side-chain carboxyl functionality. Dmpic demonstrates excellent stability under both strongly acidic and basic conditions, effectively suppresses aspartimide formation, and can be removed under mild conditions, facilitating the efficient synthesis of diverse Asp-containing lactam-cyclized peptides. Moreover, Dmpic exhibits excellent orthogonality with common protecting groups, offering a straightforward strategy for the synthesis of Asp-containing lactam-cyclized peptides.