Engineering a High-Affinity Anti-Methoxy Poly(ethylene glycol) (mPEG) Antibody for Sensitive Immunosensing of mPEGylated Therapeutics and mPEG Molecules.

Sensitive quantification of methoxy poly(ethylene glycol) (mPEG)-conjugated therapeutics for pharmacokinetic determination is critical for mPEGylated drug development. However, sensitive measurement of low-molecular-weight (lmw) mPEG compounds remains challenging due to epitope competition between backbone-specific anti-PEG antibodies. Here, we engineered a high-affinity methoxy-specific anti-mPEG antibody for sensitive quantification of free mPEG molecules and mPEGylated therapeutics. The affinity-enhanced h15-2Y antibody variant shows a 10.3-fold increase in mPEG-binding activity compared to parental h15-2b. h15-2Y-based sandwich ELISA can effectively quantify lmw mPEG5K and high-molecular-weight (hmw) mPEG20K at concentrations as low as 3.4 and 5.1 ng mL-1, respectively. Moreover, lmw mPEG compounds (560, 750, 1000, and 2000 Da) can be efficiently quantified via h15-2Y-based competitive ELISA with detection limits at nanomolar levels. This study provides a promising approach for application in the quantitative analysis of the various sizes of mPEG molecules to accelerate the timeline of mPEG-conjugated drug development.

Spatial and seasonal variations of dissolved arsenic in the Yarlung Tsangpo River, southern Tibetan Plateau.

High levels of dissolved arsenic (As) have been reported in many rivers running though the Tibetan Plateau (TP), the "Water Tower of Asia". However, the source, spatiotemporal variations, and geochemical behavior of dissolved As in these rivers remain poorly understood. In this study, hot spring, river water, and suspended particulate material samples collected from the Yarlung Tsangpo River (YTR) (upper reaches of the Brahmaputra River) system in 2017 and 2018 were analyzed. Spatial results shown that the upper reaches of YTR (Zone I) have comparatively high levels of dissolved As ([As]dissolved: mean 31.7 µg/L; 4.7-81.6 µg/L; n = 16), while the tributaries of the lower reaches (Zone II) have relatively low levels (mean 0.54 µg/L; 0.11-1.3 µg/L; n = 7). Seasonal results shown that the high [As]dissolved (6.1-22.4 µg/L) were found in September to June and low [As]dissolved (1.4-3.7 µg/L) were observed in July to August. Geothermal water is suspected as the main source of the elevated As levels in YTR due to the extremely high [As]dissolved in hot springs (1.13-9.76 mg/L) and abundance of geothermal systems throughout TP. However, the seasonal results suggested that weathering of As-containing rocks and minerals is also a key factor affecting the [As]dissolved in the river water in July to August (wet-season). Natural attenuation of As in main channel is dominated by dilution process due to the lower As concentrations in tributaries, but mostly occurred by both dilution and adsorption (or co-precipitation) processes in tributaries. This work highlights that the weathering process may have an important contribution to the dissolved As in the river waters in wet-season, and the geochemical behavior of As is largely transported conservatively in the main channel and relative non-conservatively in the tributaries in YTR system.