Inverse Peptide Synthesis Using Transient Protected Amino Acids.

Peptide therapeutics have experienced a rapid resurgence over the past three decades. While a few peptide drugs are biologically produced, most are manufactured via chemical synthesis. The cycle of prior protection of the amino group of an α-amino acid, activation of its carboxyl group, aminolysis with the free amino group of a growing peptide chain, and deprotection of the N-terminus constitutes the principle of conventional C → N peptide chemical synthesis. The mandatory use of the Nα-protecting group invokes two additional operations for incorporating each amino acid, resulting in poor step- and atom-economy. The burgeoning demand in the peptide therapeutic market necessitates cost-effective and environmentally friendly peptide manufacturing strategies. Inverse peptide chemical synthesis using unprotected amino acids has been proposed as an ideal and appealing strategy. However, it has remained unsuccessful for over 60 years due to severe racemization/epimerization during N → C peptide chain elongation. Herein, this challenge has been successfully addressed by ynamide coupling reagent employing a transient protection strategy. The activation, transient protection, aminolysis, and in situ deprotection were performed in one pot, thus offering a practical peptide chemical synthesis strategy formally using unprotected amino acids as the starting material. Its robustness was exemplified by syntheses of peptide active pharmaceutical ingredients. It is also amenable to fragment condensation and inverse solid-phase peptide synthesis. The compatibility to green solvents further enhances its application potential in large-scale peptide production. This study offered a cost-effective, operational convenient, and environmentally benign approach to peptides.

Anthropogenic Disturbance Stimulates the Export of Dissolved Organic Carbon to Rivers on the Tibetan Plateau.

The impacts of human activities on the riverine carbon (C) cycle have only recently been recognized, and even fewer studies have been reported on anthropogenic impacts on C cycling in rivers draining the vulnerable alpine areas. Here, we examined carbon isotopes (δ13CDOC and Δ14CDOC), fluorescence, and molecular compositions of riverine dissolved organic matters (DOM) in the Bailong River catchment, the eastern edge of the Tibetan Plateau to identify anthropogenic impacts on the C cycle. Human activities show limited impact on dissolved organic carbon (DOC) concentration, but significantly increased the age of DOC (from modern to ∼1600 yr B.P.) and changed the molecular compositions through agriculture and urbanization despite in the catchment with low population density. Agricultural activities indirectly increased the leaching of N-containing aged organic matter from deep soil to rivers. Urbanization released S-containing aged C from fossil products into rivers directly through wastewater. The aged DOC from agricultural activity and wastewater discharge was partly biolabile and/or photolabile. This study highlights that riverine C is sensitive to anthropogenic disturbance. Additionally, the study also emphasizes that human activities reintroduce aged DOC into the modern C cycle, which would accelerate the geological C cycle.

Constraining the sources and cycling of dissolved inorganic carbon in an alpine river, eastern Qinghai-Tibet Plateau.

It is generally acknowledged that riverine dissolved inorganic carbon (DIC) behaviors play a critical role in global carbon cycling and hence have an impact on climate change. However, little is known about the intricate DIC dynamics under various meteorological conditions in the alpine areas. Here, we investigated DIC biogeochemical processes in the Bailong River catchment, eastern Qinghai-Tibet Plateau (QTP), by combining measurements of major ions, stable and radioactive isotopic compositions of DIC (δ13CDIC and Δ14CDIC), and physiographic parameters in the Bailong River catchment. Statistics and stoichiometry analyses suggest that multiple biogeochemical processes could affect carbon cycling in the Bailong River catchment. The "old" DIC with low Δ14C values (-472.4 ± 127.8 ‰, n = 3) and stoichiometry analysis of dissolved ions showed clear evidence that carbonate weathering is primarily responsible for water chemistry in the upstream (elevation >2000 m). However, upstream samples showed that δ13CDIC increased between 5 ‰ and 11 ‰ from the theoretical mixing line, concomitant with increasing pH and decreasing pCO2, suggesting that isotopic fractionation of DIC due to CO2 outgassing may be the primary cause of the increased δ13CDIC values. Additionally, the higher Δ14C values (-285.4 ± 123.5 ‰, n = 12) in the downstream region below 2000 m suggest that allochthonous modern carbon had a great impact on DIC variations. The presence of younger DIC may have important implications for the interpretation of inorganic carbon age in downstream rivers. Our study demonstrates that physiographic conditions can regulate DIC behaviors, which can improve estimations of carbon yield and comprehension of global carbon cycle.

[Accelerated Degradation of Aqueous Recalcitrant Iodinated Contrasting Media Using a UV/SO32- Advanced Reduction Process].

Based on the formation of free radical-hydrated electrons by the activation of sulfite (SO32-), the UV/SO32- process is an advanced reduction process that can reduce pollutants. This study investigated the degradation kinetics, mechanism, influencing factors, and degradation pathways of sodium diatrizoate (DTZ), an iodinated contrasting media, during the UV/SO32- process. The degradation kinetics of DTZ were well fitted by the pseudo-first-order model, the degradation rate of which was higher than that of UV only and UV/H2 O2. The degradation rate of DTZ during the UV/SO32- process was positively correlated with the initial SO32- concentration. Weakly alkaline and alkaline conditions promoted the degradation of DTZ, while organic matter inhibited degradation during the UV/SO32- process. The degradation mechanism included direct photolysis and free radical attack, whereby free radical attack played a more important role than direct photolysis. Sulfite radicals dominated DTZ degradation efficiency, and hydrated electrons controlled the deiodination efficiency. The degradation pathways of DTZ during the UV/SO32- process included substitution, decarboxylation-hydroxylation, and amide bond cleavage.