Iminoboronate-Mediated Peptide Cyclization with Lysine Homologues

Cyclic peptides are attracting attention of medicinal chemists due to their increased stability in biological milieu as well as improved target binding affinities. Our laboratory has recently reported a powerful cyclization strategy that takes advantage of the spontaneous and reversible conjugation of lysine and a designed amino acid AB3 to give iminoboronates. Herein we report that Dap, a short chain homologue of lysine, displays significantly higher propensity to form iminoboronates and consequently improves the efficiency of peptide cyclization. Importantly, the preferential conjugation of AB3 to Dap allows a facile synthesis of cyclic peptides with free lysine residues.