Functionalized HgTe nanoparticles promote laser-induced solid phase ionization/dissociation for comprehensive glycan sequencing

Abstract

Glycoconjugates are ubiquitously present and play a critical role in various biological processes. Due to their low stability and incredibly high degree of structural diversity, the structural characterization of glycan generally requires chemical derivatization and sophisticated instrumentation. Herein, we report a method for complicated glycan characterization in a single assay by employing 2,5-dihydroxybenzoic acid functionalized mercury telluride nanoparticles (HgTe@DHB NPs) as a dual ionization-dissociation element in matrix-assisted laser desorption/ionization mass spectrometry. Using a linear glycan, HgTe@DHB NPs promote laser-induced extensive and intense dissociation of the glycan, superior to HgTe microparticles and other inorganic nanoparticles (TiO, ZnO, and MnO NPs). Abundant generation of diagnostic glycosidic (Y-, and B-type ions) and cross-ring cleavage (A-type ions) ions permits unambiguous determination of the composition, sequence, branching, and linkage of labile sialylated glycans. The general utility of this approach was demonstrated by the characterization of labile sialylated glycans and two sets of complicated isomeric glycans. This phenomenon was delineated further by investigating the NP's physico-chemical characteristics, revealing that their nanoscale-dependent thermodynamic properties, including UV absorption, photoelectron release dynamics and thermal energy, were the key to levitate temperature synergistically, thus inducing spontaneous glycan decomposition during the nanoparticle-assisted laser desorption-ionization process. Our results show that this "pseudo-MS/MS" obtained by HgTe@DHB can be beneficial for the analysis of biologically relevant and more complicated carbohydrates, without the need for chemical pre-derivatization and conventional tandem mass spectrometry.

Mass spectrometry for protein sialoglycosylation

“…Accordingly, a detailed structural analysis of oligosaccharides is possible and HCD allows for distinguishing isomeric glycans with different sialic acid linkages. In addition, a nanoparticle‐assisted matrix has recently been employed for MALDI‐MS analysis of sialoglycans . Nanoparticles can transfer thermal energy for the ionization and dissociation of analytes.…”

“…In addition, a nanoparticle-assisted matrix has recently been employed for MALDI-MS analysis of sialoglycans. 315 Nanoparticles can transfer thermal energy for the ionization and dissociation of analytes. As a result, the nanoparticle-assisted matrix is helpful for producing fragment ions via an ISD-like process.…”

Nanomaterials as Assisted Matrix of Laser Desorption/Ionization Time-of-Flight Mass Spectrometry for the Analysis of Small Molecules

“…Among various metal-or metal oxide-based nanomaterials (e.g., Au [51,52,53,54,55], Ag [56], Pt [57,58,59], TiO 2 [60,61,62], ZnO [63], CdS [64], and HgTe [65] NPs) that explored as matrices for LDI-TOF MS, TiO 2 and gold NPs (Au NPs) attracted much more attention because their intrinsic advantages, such as large surface area, strong absorption efficiency in UV-visible region, high chemical stability, easy modification and preparation.…”

Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry: Mechanistic Studies and Methods for Improving the Structural Identification of Carbohydrates

“…157,158) Akin to an ISD process, functionalized nanoparticles release charges and redistribute energy that facilitate fragmentation a er absorbing laser energy. 122) Our group synthesized DHB-functionalized mercury telluride nanoparticles (HgTe@DHB NPs) as a novel matrix, which induced both glycosidic and cross-ring cleavages in the solid phase. is method allowed us to do pseudo-MS/MS in a single step by regulating amounts of HgTe@DHB.…”

“…Charge and energy transfer from NPs to analytes triggers ionization/fragmentation and desorption of carbohydrates. 117,122) Furthermore, functionalization of NPs with conventional organic matrices have been reported to serve as new matrix materials to preserve the intact glycan as well as the generation of extensive cleavages in MALDI. 123) More details about methods on the structural identi cation of carbohydrates are reviewed in the following section.…”