Tailoring isomeric transformations and surface adsorption dynamics of glycopeptides under thermal and photolytic stress #MMPMID41389152
Paritala ST; Ingle P; Shah RP; Sharma N
Anal Bioanal Chem 2025[Dec]; ? (?): ? PMID41389152show ga
Dalbavancin, unlike other peptides administered through the IV route, is highly influenced by subtle environmental shifts. These shifts may alter the primary structure and trigger immunogenic reactions leading to reduced efficacy and safety. Hence, there is a critical need to investigate the factors influencing dalbavancin. In this respect, the behavior of dalbavancin under heat and light was studied. Eight degradation products were identified after the thermal and photolytic exposure of dalbavancin. Using tandem mass spectrometric studies (MS(n)), the degradation products and mechanistic pathways for the construction of these degradation products were identified. The formation of four isomeric degradation products was especially identified under thermal stress conditions. Further elucidation and characterization of isomeric degradation products were processed through 3D energy minimization approaches. Glycan and the modified N-terminus were translated as plausible isomeric soft spots altering the primary structure of dalbavancin. In photolytic conditions under visible light, four degradation products were identified, where epoxidation and hydroxylation were identified as the major mechanistic pathways. Especially under UV light, dalbavancin was adsorbed on the surfaces of the storage containers. Through FE-SEM investigations, the phenomenon of self-assembly for the adsorbed particles was identified. Further EDAX studies confirmed the surface interaction where chlorine, a key distinguishing element of dalbavancin, was identified on the surfaces exposed to UV light. These results collectively suggest dalbavancin is highly vulnerable to environmental conditions altering its primary structure and emphasizing the need for proper storage conditions during handling, usage, and the development of similar therapeutics.
Anal+Bioanal+Chem 2025 ; ? (?): ?
