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

Summary 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, theC ^α-carboxyl of which forms an, amide with theN ^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. Taken in part from the Ph.D. Thesis of J. C. Kappel, University of Minnesota, November 2003. Portions of this work were reported in preliminary form at the Eighteenth American Peptide Symposium, Boston, MA, U.S.A., 19–23 July 2003, and at the Eighth International Symposium on Solid Phase Synthesis and Combinatorial Chemical Libraries, London, England, U.K., 2–5 September 2003.