Experimentally Determined Site-Specific Reactivity of the Gas-Phase OH and Cl + i-Butanol Reactions Between 251 and 340 K

2016 ◽  
Vol 120 (50) ◽  
pp. 9968-9981 ◽  
Author(s):  
Max R. McGillen ◽  
Geoffrey S. Tyndall ◽  
John J. Orlando ◽  
Andre S. Pimentel ◽  
Diogo J. Medeiros ◽  
...  
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.


2015 ◽  
Vol 10 (1) ◽  
pp. 122-128 ◽  
Author(s):  
Josue Baeza ◽  
Michael J. Smallegan ◽  
John M. Denu

1994 ◽  
Vol 86 (s30) ◽  
pp. 11P-11P ◽  
Author(s):  
JE Smithson ◽  
C Prince ◽  
R Pigott ◽  
DP Jewell

2007 ◽  
Vol 1002 ◽  
Author(s):  
Chad R Barry ◽  
Uwe Kortshagen ◽  
Heiko O Jacobs

ABSTRACTWe report on two gas phase nanoparticle integration processes to assemble nanomaterials onto desired areas on a substrate. We expect these processes to work with any material that can be charged. The processes offer self-aligned integration and could be applied to any nanomaterial device requiring site specific assembly. The Coulomb force process directs the assembly of nanoparticles onto charged surface areas with sub-100 nm resolution. The charging is accomplished using flexible nanostructured electrodes. Gas phase assembly systems are used to direct and monitor the assembly of nanoparticles onto the charge patterns with a lateral resolution of 50 nm. The second concept makes use of fringing fields. The fringing fields directed the assembly of nanoparticles into openings. The fringing fields can be confined to sub 50 nm sized areas and exceed 1 MV/m, acting as nanolenses. Gas phase assembly systems have been used to deposit silicon, germanium, metallic, and organic nanoparticles.


ChemCatChem ◽  
2018 ◽  
Vol 10 (2) ◽  
pp. 335-335
Author(s):  
Anita Godiksen ◽  
Oliver L. Isaksen ◽  
Søren B. Rasmussen ◽  
Peter N. R. Vennestrøm ◽  
Susanne Mossin

Author(s):  
M.T. Rodgers ◽  
Sherrie Campbell ◽  
Elaine M. Marzluff ◽  
J.L. Beauchamp
Keyword(s):  

ChemPhysChem ◽  
2017 ◽  
Vol 18 (4) ◽  
pp. 357-365 ◽  
Author(s):  
Josua Pecher ◽  
Gerson Mette ◽  
Michael Dürr ◽  
Ralf Tonner

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