The study suggests that PABC helped Veterans after TKA increase and sustain the duration of daily brisk cadence walking. Future investigations should incorporate the PABC to explore potential interven...

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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 Å2, all lower than that of the Lys188 model (1524 Å2). Thus, the more stable comparator exhibited the highest modeled exposure. This mismatch between modeled exposure and observed release argues against a simple exposure-driven cleavage mechanism as the primary explanation for the wild-type behavior. Instead, the results suggest that the observed payload release is influenced by bond chemistry in addition to linker exposure.

During the month of June, faculty and graduate students from the Department of Anthropology were in Chiapas, Mexico for fieldwork as part of the Proyecto Arqueológico Busiljá-Chocoljá (PABC).