Identification, occurrence and prevention of aspartimide-related byproducts in chemical protein synthesis.

ABSTRACT: Formation of a five-membered ring aspartimide through the attack of a backbone amide to the side chain of aspartate and asparagine residues is a long-known side-reaction in solid phase peptide synthesis, and is also associated with in vivo protein ageing and instability of purified proteins. Conversely, its possible occurrence during chemical ligation-based protein synthesis, in particular when using the gold-standard reaction NCL (native chemical ligation), is dubious. We herein report a systematic study which demonstrates that the prevalence of this side-reaction may have been overlooked, due to the difficulty to identify it through standard HPLC analytical methods, but also the in situ conversion of aspartimide into other byproducts, having the same molecular mass as the p

SUBMITTER: Cisse EH 

PROVIDER: S-EPMC12262139 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature