scholarly journals Multidimensional mass spectrometry characterization of isomeric biodegradable polyesters

2017 ◽  
Vol 23 (6) ◽  
pp. 402-410 ◽  
Author(s):  
Sahar Sallam ◽  
Yuanyuan Luo ◽  
Matthew L Becker ◽  
Chrys Wesdemiotis

The biodegradable polyester copolymer poly(propylene fumarate) (PPF) is increasingly utilized in bone tissue engineering studies due to its suitability as inert cross-linkable scaffold material. The well-defined poly(propylene fumarate) oligomers needed for this purpose are synthesized by post-polymerization isomerization of poly(propylene maleate), which is prepared by ring opening polymerization of maleic anhydride and propylene oxide. In this study, multidimensional mass spectrometry methodologies, interfacing matrix-assisted laser desorption ionization and electrospray ionization with mass analysis, tandem mass spectrometry fragmentation and/or ion mobility mass spectrometry, have been employed to characterize the composition, end groups, chain connectivity and isomeric purity of the isomeric copolyesters poly(propylene maleate)and poly(propylene fumarate). It is demonstrated that the polymerization catalyst is incorporated into the polymer chain (as the initiating chain end) and that the poly(propylene maleate) to poly(propylene fumarate) isomerization using an amine base proceeds with quantitative yield. Hydrolytic degradation is shown not to alter the double bond geometry of the poly(propylene fumarate) or poly(propylene maleate) chains.

Separations ◽  
2021 ◽  
Vol 8 (3) ◽  
pp. 33
Author(s):  
Xavier Garcia ◽  
Maria del Mar Sabaté ◽  
Jorge Aubets ◽  
Josep Maria Jansat ◽  
Sonia Sentellas

This paper aims to cover the main strategies based on ion mobility spectrometry (IMS) for the analysis of biological samples. The determination of endogenous and exogenous compounds in such samples is important for the understanding of the health status of individuals. For this reason, the development of new approaches that can be complementary to the ones already established (mainly based on liquid chromatography coupled to mass spectrometry) is welcomed. In this regard, ion mobility spectrometry has appeared in the analytical scenario as a powerful technique for the separation and characterization of compounds based on their mobility. IMS has been used in several areas taking advantage of its orthogonality with other analytical separation techniques, such as liquid chromatography, gas chromatography, capillary electrophoresis, or supercritical fluid chromatography. Bioanalysis is not one of the areas where IMS has been more extensively applied. However, over the last years, the interest in using this approach for the analysis of biological samples has clearly increased. This paper introduces the reader to the principles controlling the separation in IMS and reviews recent applications using this technique in the field of bioanalysis.


2021 ◽  
Vol 14 (6) ◽  
pp. 498
Author(s):  
Evolène Deslignière ◽  
Anthony Ehkirch ◽  
Bastiaan L. Duivelshof ◽  
Hanna Toftevall ◽  
Jonathan Sjögren ◽  
...  

Antibody-drug conjugates (ADCs) are biotherapeutics consisting of a tumor-targeting monoclonal antibody (mAb) linked covalently to a cytotoxic drug. Early generation ADCs were predominantly obtained through non-selective conjugation methods based on lysine and cysteine residues, resulting in heterogeneous populations with varying drug-to-antibody ratios (DAR). Site-specific conjugation is one of the current challenges in ADC development, allowing for controlled conjugation and production of homogeneous ADCs. We report here the characterization of a site-specific DAR2 ADC generated with the GlyCLICK three-step process, which involves glycan-based enzymatic remodeling and click chemistry, using state-of-the-art native mass spectrometry (nMS) methods. The conjugation process was monitored with size exclusion chromatography coupled to nMS (SEC-nMS), which offered a straightforward identification and quantification of all reaction products, providing a direct snapshot of the ADC homogeneity. Benefits of SEC-nMS were further demonstrated for forced degradation studies, for which fragments generated upon thermal stress were clearly identified, with no deconjugation of the drug linker observed for the T-GlyGLICK-DM1 ADC. Lastly, innovative ion mobility-based collision-induced unfolding (CIU) approaches were used to assess the gas-phase behavior of compounds along the conjugation process, highlighting an increased resistance of the mAb against gas-phase unfolding upon drug conjugation. Altogether, these state-of-the-art nMS methods represent innovative approaches to investigate drug loading and distribution of last generation ADCs, their evolution during the bioconjugation process and their impact on gas-phase stabilities. We envision nMS and CIU methods to improve the conformational characterization of next generation-empowered mAb-derived products such as engineered nanobodies, bispecific ADCs or immunocytokines.


2016 ◽  
Vol 89 (2) ◽  
pp. 1170-1177 ◽  
Author(s):  
Ahlam Alalwiat ◽  
Wen Tang ◽  
Selim Gerişlioğlu ◽  
Matthew L. Becker ◽  
Chrys Wesdemiotis

2018 ◽  
Vol 90 (24) ◽  
pp. 14453-14461 ◽  
Author(s):  
Tiffany M. Crescentini ◽  
Sarah M. Stow ◽  
Jay G. Forsythe ◽  
Jody C. May ◽  
John A. McLean ◽  
...  

2021 ◽  
Vol 12 ◽  
Author(s):  
Kai P. Law ◽  
Wei He ◽  
Jianchang Tao ◽  
Chuanlun Zhang

Archaea are differentiated from the other two domains of life by their biomolecular characteristics. One such characteristic is the unique structure and composition of their lipids. Characterization of the whole set of lipids in a biological system (the lipidome) remains technologically challenging. This is because the lipidome is innately complex, and not all lipid species are extractable, separable, or ionizable by a single analytical method. Furthermore, lipids are structurally and chemically diverse. Many lipids are isobaric or isomeric and often indistinguishable by the measurement of mass or even their fragmentation spectra. Here we developed a novel analytical protocol based on liquid chromatography ion mobility mass spectrometry to enhance the coverage of the lipidome and characterize the conformations of archaeal lipids by their collision cross-sections (CCSs). The measurements of ion mobility revealed the gas-phase ion chemistry of representative archaeal lipids and provided further insights into their attributions to the adaptability of archaea to environmental stresses. A comprehensive characterization of the lipidome of mesophilic marine thaumarchaeon, Nitrosopumilus maritimus (strain SCM1) revealed potentially an unreported phosphate- and sulfate-containing lipid candidate by negative ionization analysis. It was the first time that experimentally derived CCS values of archaeal lipids were reported. Discrimination of crenarchaeol and its proposed stereoisomer was, however, not achieved with the resolving power of the SYNAPT G2 ion mobility system, and a high-resolution ion mobility system may be required for future work. Structural and spectral libraries of archaeal lipids were constructed in non-vendor-specific formats and are being made available to the community to promote research of Archaea by lipidomics.


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