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Start Over Author "Zhang Guodong" Publisher american chemical society
121 results on '"Zhang Guodong"'

28. Strategies for bioanalysis of an oligonucleotide class macromolecule from rat plasma using liquid chromatography--tandem mass spectrometry

Author

Zhang, Guodong, Lin, Jian, Srinivasan, Karthik, Kavetskaia, Olga, and Duncan, J. Neil

Subjects
Mass spectrometry -- Research, Liquid chromatography -- Usage, Macromolecules -- Research, Nucleotides -- Research, Rats -- Research, Rattus -- Research, Chemistry
Abstract

Electrospray ionization (ESI) liquid chromatography-tandem mass spectrometry (LC/MS/MS) assays provide high-throughput and selective methods for quantitation of small molecules. Use of LC/MS/MS assays for macromolecules, like oligonucleotides, is challenging due to lack of sensitivity and low analyte recovery from biomatrixes. Due to this fact, the method of choice for oligonucleotides quantitation remains hybridization-based ligand-binding assays. These biological assays usually possess high sensitivity but low selectivity and narrow dynamic range. They also require optimizing suitable 'capture and detection' probes, which can be prohibitively time-consuming and expensive in a drug discovery lead--optimization scenario. In this paper, we present a unique LC/MS/MS assay for a model phosphorothioate backbone oligodeoxynucleotide (ODN) drug (7692 amu) from rat plasma. Multiple analytical challenges were encountered. The strategies used to solve these challenges should prove useful to scientists pursuing mass spectrometry (MS) to quantitate oligonucleotides. The challenges include analyte multiple charging and cation adduction (reduced sensitivity), oxidation of analyte on drying and high protein binding (low recovery), ODN affinity to exposed silica (low chromatographic reproducibility and high carryover), nonspecific binding of analyte to containers (low storage stability), and optimization/synthesis of an appropriate internal standard (interference and cross-talk). A buffer (7 mM triethylamine and 3 mM ammonium formate)/ methanol, 50:50 (v/v), was used as an ESI-MS infusion solvent and produced a sharp multiple charge-state distribution. The sample extraction method combined a phenol/chloroform liquid-liquid extraction and solid-phase extraction steps, which improved the absolute recovery to > 70%. The method was validated in the range of 5-2000 ng/mL and had precision (percent relative standard deviation) < 10.1% and accuracy (percent relative error) < 11.4%.

Published
2007

49. Mn-Mn Dimers Induced Multimode Emitters in Mn 2+ -Activated AZn 4 (PO 4 ) 3 (A = K, Rb, and Cs) with Unique [Zn 4 PO 12 ] Chains and [ZnO n ] Groups.

Author

Liu Q, Dang P, Zhang G, Lian H, Cheng Z, Li G, and Lin J

Abstract

Mn 2+ -doped luminescent materials play a significant role in a variety of fields, including modern lighting, displays, and imaging. Mn 2+ exhibits a broad and adjustable emission, hinging on the local environment of the crystal field and the interaction of the 3d 5 electrons. However, it is still a challenge to realize the precise control of the emission of Mn 2+ ions due to site-prior occupation in a specific lattice. Here, the formation of Mn-Mn dimers is proposed to be an effective strategy to design a novel red emission. Multimode emitters in Mn 2+ -activated AZn 4 (PO 4 ) 3 (A = K, Rb, and Cs) with unique [Zn 4 PO 12 ] chains and [ZnO n ] groups are observed to achieve regular green and unusual red emissions. KZn 4 (PO 4 ) 3 :Mn 2+ shows broad dual emissions at 542 and 608 nm, attributed to [MnO 4 ] and [Mn 2 O 7 ] dimers, respectively. While K is replaced with Rb and Cs, the Zn ions form [ZnO 4 ] tetrahedra and [ZnO 5 ] octahedra. RbZn 4 (PO 4 ) 3 :Mn 2+ exhibits a broad red emission at 618 nm, ascribing to [Mn 2 O 7 ] and [Mn 2 O 8 ] dimers. CsZn 4 (PO 4 ) 3 :Mn 2+ also displays a broad orange-red emission at 608-620 nm with increasing doping levels, deriving from energy transfer from [MnO 5 ] to [Mn 2 O 7 ] and [Mn 2 O 8 ] dimers. This work provides a framework for creating novel red emissions from Mn 2+ -doped luminescent materials.

Published
2025
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50. Discovery of N -Phenyl-5-propyl-1 H -pyrazole-3-carboxamide, with Selective Inhibition and Degradation of HDAC6 for the Treatment of Acute Liver Injury.

Author

Cui H, Zhang G, Zhang L, Sun S, Yang K, Gen A, Wang P, Wang H, Zhou QQ, Li H, Chen Y, Yao Y, Lu T, Zhang L, and Zhu Y

Subjects
Animals, Mice, Humans, Male, Structure-Activity Relationship, Drug Discovery, Acetaminophen, Mice, Inbred C57BL, Histone Deacetylase 6 antagonists & inhibitors, Histone Deacetylase 6 metabolism, Histone Deacetylase Inhibitors pharmacology, Histone Deacetylase Inhibitors chemistry, Histone Deacetylase Inhibitors chemical synthesis, Histone Deacetylase Inhibitors therapeutic use, Pyrazoles pharmacology, Pyrazoles chemistry, Pyrazoles chemical synthesis, Pyrazoles therapeutic use, Chemical and Drug Induced Liver Injury drug therapy, Chemical and Drug Induced Liver Injury pathology
Abstract

Acute liver injury is a severe and potentially life-threatening condition. Currently, there are no specific effective treatments available. HDAC6 has been identified as a promising strategy for treating ALI by inhibiting necrosis and inflammation. In this study, a series of pyrazole derivatives were designed to specifically target HDAC6, among which compound 6 demonstrated high antinecroptotic activity (IC 50 = 0.5 nM) and excellent selective HDAC6 inhibition (IC 50 = 4.95 nM, HDAC1/HDAC6 = 251). Surprisingly, compound 6 also exhibited excellent HDAC6 degradation activity (DC 50 = 0.96 nM) through mechanistic studies. Additionally, it demonstrated strong inhibitory effects on inflammatory proteins TNF-α, IL-1β, and IL-6, indicating significant anti-inflammatory activity. Moreover, in a mouse model of acetaminophen (APAP)-induced acute liver injury, compound 6 exhibited significant therapeutic and protective efficacy at a dose of 40 mg/kg. These findings confirm that compound 6 is a promising lead structure for combating ALI-related diseases and warrants further investigation.

Published
2025
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