FIGURE 4.

Schematic representation of potential cyclic and linear NGR peptide degradation reactions. A, nucleophilic attack of the backbone NH center (blue) on the Asn side chain (red) of cyclic CNGRC leads to formation of a succinimide intermediate (−17 Da), which after hydrolysis may lead to formation of Asp and isoAsp (+1 Da). B, succinimide formation and hydrolysis can occur also with linear GNGRG. However in this case, the succinimide intermediate may also react with α-amino group leading to the formation of seven-membered ring or diketopiperazine (DKP).