SIDE REACTIONS IN SYNTHESIS OF PEPTIDES CONTAINING ASPARTYLGLYCYL SEQUENCE

The hexapeptides L-histidyl-L-seryl-L-aspar-tylglycyl-L-threonyl-L-phenylalanine (1) and L-histidyl- L - seryl-β - 1 - aspartylglycyl - L - threonyl-L-phenylalanine (2) have been synthesized by the standard procedures of peptide synthesis. When the preparation of the same hexapeptides was attempted by the solid-phase approach, the only major product isolated was the succinimido derivative, namely, L-histidyl-L-seryl-L-aspartimidylglycyl-L-threonyl-L-phenylalanine (13). Formation of succinimido derivatives was also observed during the synthesis of 1 by the standard procedure, but only when the β- carboxyl group of aspartic acid was esterified. The lack of a side chain in the glycyl residue appears to be the most important contributing factor to the pronounced tendency of the aspartylglycine sequence to rearrange through the formation of cyclic imide intermediates. © 1968, American Chemical Society. All rights reserved.