Schultz Parsons (ideadonkey04)

The results reveal that the secondary ligand is the guide toward the mode of binding between the copper complex and DNA in which glycinate prefers minor-groove binding and acetylacetonate produces base-pair eversion and intercalation. The CuII complexes containing glycinate interact within the DNA minor groove which are stabilized principally by the hydrogen bonds formed between the amino group of the aminoacidate moiety, whereas the compounds with the acetylacetonate do not present a stable network of hydrogen bonds and the ligand interactions enhance DNA breathing dynamics that result in base-pair eversion.Two rearranged nardosinane sesquiterpenoids with novel carbon skeletons, lemnardosinanes A (1) and B (2), and seven new nardosinane-related sesquiterpeniod lemnardosinanes C-I (3-9), together with a known compound 6,7-seco-13-nornardosinan (10), were isolated from the soft coral Lemnalia sp. collected from Xisha Islands of the South China Sea. Their structures were elucidated by comprehensive spectroscopic analyses, Mosher's method, Mo2(OAc)4-induced circular dichroism experiment, and quantum chemical calculations. Plausible biosynthetic pathways of 1-10 were proposed. Compounds 1 and 10 displayed in vivo angiogenesis promoting activity in a zebrafish model. selleck chemicals llc Compounds 3 and 4 exhibited antiviral activity against the H1N1 virus with IC50 values of 10.9 and 41.5 μM, respectively.The SARS coronavirus 2 (SARS-CoV-2) main protease (Mpro) is an attractive broad-spectrum antiviral drug target. Despite the enormous progress in structure elucidation, the Mpro's structure-function relationship remains poorly understood. Recently, a peptidomimetic inhibitor has entered clinical trial; however, small-molecule orally available antiviral drugs have yet to be developed. Intrigued by a long-standing controversy regarding the existence of an inactive state, we explored the proton-coupled dynamics of the Mpros of SARS-CoV-2 and the closely related SARS-CoV using a newly developed continuous constant pH molecular dynamics (MD) method and microsecond fixed-charge all-atom MD simulations. Our data supports a general base mechanism for Mpro's proteolytic function. The simulations revealed that protonation of His172 alters a conserved interaction network that upholds the oxyanion loop, leading to a partial collapse of the conserved S1 pocket, consistent with the first and controversial crystal structure of SARS-CoV Mpro determined at pH 6. Interestingly, a natural flavonoid binds SARS-CoV-2 Mpro in the close proximity to a conserved cysteine (Cys44), which is hyper-reactive according to the CpHMD titration. This finding offers an exciting new opportunity for small-molecule targeted covalent inhibitor design. Our work represents a first step toward the mechanistic understanding of the proton-coupled structure-dynamics-function relationship of CoV Mpros; the proposed strategy of designing small-molecule covalent inhibitors may help accelerate the development of orally available broad-spectrum antiviral drugs to stop the current pandemic and prevent future outbreaks.Residual pesticides in soil may be taken up by crops and negatively affect food safety. The uptake mechanism of imidacloprid and propiconazole was studied using wheat roots. The factors affecting root uptake were also studied with different crops and in different soils. Imidacloprid and propiconazole were taken up by wheat roots mainly through the symplastic and apoplastic pathways, respectively. Root protein and lipid contents were the main factors affecting the uptake and accumulation of imidacloprid and propiconazole by different crop roots, respectively. The uptake of imidacloprid and propiconazole in soil by wheat plants was linearly correlated with their concentrations in soil pore water, which were governed by soil characteristics. These results are helpful for understanding and estimating crop uptake of residual pesticides in soils.A dual experimental/t