Methionine anchoring applied to the solid-phase synthesis of lysine-containing 'head-to-tail' cyclic peptides

Lysine-containing 'head-to-tail' cyclic peptides can be prepared via a side-chain anchoring solid-phase synthesis strategy. A handle is prepared using a methionine residue, the C^α-carboxyl of which forms an amide with the N^ε-amine of lysine. Subsequently, the linear peptide sequence is assembled, appropriate deblocking steps are carried out, and on-resin head-to-tail cyclization follows. Optionally, acid-labile protecting groups may be removed while the peptide remains resin-bound. The final cleavage step uses CNBr, and releases the free or protected cyclic peptide into solution.