ArticleBiomedical chromatography : BMC2026
LC-MS/MS Quantification and Solvent-Exposure Modeling Reveal a Mismatch Between Linker Exposure and Payload Release in Wild-Type Trastuzumab-VC-PABC-MMAE in Rat Plasma.
Article in Biomedical chromatography : BMC, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Authors and funding
3 authors.
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Abstract
Free monomethyl auristatin E (MMAE) released from trastuzumab-valine-citrulline-p-aminobenzyl carbamate (VC-PABC)-MMAE conjugates was quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) after incubation in rat plasma at 37°C for 4 days. A wild-type conjugate prepared by maleimide-thiol interchain cysteine conjugation showed 4% ± 3.5% release (n = 3 for each), whereas a Lys188-selective comparator prepared by click chemistry after lipoic acid ligase A-mediated modification showed 4% ± 3.5% release. To examine whether this difference could be explained by linker-payload exposure, molecular dynamics simulations were performed, and solvent-accessible surface areas (SASA) were calculated for representative wild-type interchain cysteine environments and for the Lys188 conjugate. Mean SASA values for the wild-type models were 1132-1293 Å
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