Recent progress of protein glycosylation characterization utilizing native conformer-resolved mass spectrometry / 中国药科大学学报

@#Glycosylation of proteins, one of the most prevalent and complex post-translational modifications occurring in nature, plays a crucial role in regulating protein net charge, conformation, binding properties and, ultimately, biological function.Traditional structural techniques are not amenable for glycoproteins due to the inherent heterogeneity of oligosaccharides.With the advances in analytical technique, mass spectrometry displays an increasingly crucial role in elucidating the structure of glycoproteins.Mass spectrometry-based proteomic technique can dissect the chemical composition and site information of low-abundance glycosylation at the peptide level.Instead, native mass spectrometry (nMS) can analyze intact glycoproteins while maintaining the information for glycan heterogeneity, and the insights into the regulatory effects of glycosylation on protein higher order structures and interactions with other proteins or ligands.As a representative structural mass spectrometry tool, ion mobility-based nMS strategy is powered by its conformer-resolving capability and by the feasibility of conformer manipulation through collision-induced unfolding.Consequently, native IM-MS analysis can provide rich information of dynamic protein conformations, allowing for the rapid identification and differentiation of protein isoforms in an unprecedented manner.In this review, we briefly introduced two emerging native IM-MS analytical modes, dynamic conformer-resolving mode and glycoform-resolving mode.Besides, we also discussed the recent progress of conformational and topological characterization of intact glycoproteins with three typical model systems based on two above-mentioned emerging modes of native IM-MS.

Applications of BGUSs inhibition in tumor prevention and chemotherapy / 中国临床药理学与治疗学

Bacterial β-glucuronidases (BGUSs) are an important type of hydrolase produced by gut microbiota and play an important role in tumor development and chemotherapy by deconjugating a large number of endogenous and exogenous glucuronides. In recent years, BGUSs inhibition has emerged as a promising approach to reduce cancer risk and alleviate gastrointestinal toxicity of chemotherapy drugs. However, a growing body of evidence underlines great genetic and structural diversity, functional promiscuity, and varied inhibition propensity of BGUSs, which have posed enormous challenges to identifying BGUSs involved in a specific pathophysiological or pharmacological process and developing effective inhibitors. In this review, we summarize the latest advances in structure and function of BGUSs and review the findings of BGUSs-mediated carcinogen reactivation and deconjugation of chemotherapy drugs in recent years, as well as the discovery of BGUSs inhibitors and preclinical investigation of their applications in cancer prevention and drug therapy. Finally, we discuss the prospects of BGUSs inhibition as a new strategy for tumor prevention and drug therapy.