Influence of Methylating the Serine Side Chain on the Decomposition of Protonated Asparaginyl Serine: GIBMS, IRMPD, and Theoretical Modeling Studies

This study examines the decomposition of the protonated dipeptide, AsnSer methylated on the serine side chain, Asn(OMe)Ser. We utilize threshold collision-induced dissociation (TCID) conducted on a guided ion beam tandem mass spectrometer (GIBMS) to examine the deamidation and dehydration from [Asn(OMe)Ser+H] + . We also use infrared multiple-photon dissociation (IRMPD) spectroscopy to verify the reactant and product structures. These experimental analyses are reported in parallel with complementary quantum-chemical calculations, where key reaction energies are determined at the B3LYP, ωB97XD, and MP2(full) levels of theory. Comparison of IRMPD and theoretical spectra identifies the major deamidation product as a furanone with a probable contribution of a succinimide. Dehydration occurs through the formation of multiple products, but we assign the primary product to be a diketopiperazine along with a minor contribution from a pyrrolidone. The TCID data were modeled and the results show that deamidation begins at 141 ± 7 kJ/mol and dehydration at 121 ± 7 kJ/mol. Compared to the unmethylated analogue, the deamidation threshold is comparable whereas that for dehydration is elevated, consistent with methylation shutting down the lowest-energy pathway for dehydration of [AsnSer+H] +, previously shown to form an oxazoline product ion.