Reversible Macrocyclization of Peptides with a Conjugate Acceptor.

Macrocyclic peptides are an increasingly important class of biopharmaceuticals. A new method of macrocyclization is reported that involves reaction of the N-terminal amine and thiol side chain of cysteine with a Meldrum's acid derived conjugate acceptor. This reaction, which utilizes naturally occurring amino acids and requires no orthogonal protection of side chains, can also be reversed to yield the original linear peptide as desired.