Isoacyl Dipeptides

Isoacyl dipeptides can be formed on resin, but the conditions required for coupling can produce significant levels of racemization in the acyl amino acid. Isoacyl dipeptides can be formed in solution phase, however, nearly racemization-free (Y. Sohma, et al. Tetrahedron Lett. 2006, 47, 3013-7; T. Yoshiya, et al. Org. Biomol. Chem. 2007, 5, 1720-30). Thus to avoid racemization, isoacyl peptides are synthesized utilizing preformed isoacyl dipeptides to introduce the isoacyl peptide bond, followed by conventional solid phase peptide synthesis protocols. Diketopiperazine formation has been reported in some instances, but this can be prevented by using Bsmoc-protected amino acids for the first coupling onto isoacyl peptides.(J. Coin, et al. Nature Protocols 2007, 2, 3247-56.)

Isoacyl dipeptides are also useful tools for segment condensation. Incorporated as the C-terminus of the N-segment, isoacyl dipeptides allow peptide segments to be coupled with very little racemization of the activated amino acid residue. After forming the isopeptide by segment coupling, rearrangement through the acyl shift results in the desired peptide. (T. Yoshiya, et al. Tetrahedron Lett. 2006, 47, 7095-9).