A5100698990- DNA Repair Mechanisms
- Epigenetics and DNA Methylation
- DNA and Nucleic Acid Chemistry
- RNA modifications and cancer
- Metal-Catalyzed Oxygenation Mechanisms
- RNA and protein synthesis mechanisms
- Coordination Chemistry and Organometallics
- Bacteriophages and microbial interactions
- Carcinogens and Genotoxicity Assessment
- Advanced biosensing and bioanalysis techniques
- Metalloenzymes and iron-sulfur proteins
- Advanced NMR Techniques and Applications
- Molecular spectroscopy and chirality
- HIV/AIDS drug development and treatment
- Folate and B Vitamins Research
- Radical Photochemical Reactions
- Lower Extremity Biomechanics and Pathologies
- Catalytic C–H Functionalization Methods
- Antibiotic Resistance in Bacteria
- Osteoarthritis Treatment and Mechanisms
- Cancer-related gene regulation
- Protein Structure and Dynamics
- Antimicrobial Peptides and Activities
- Cancer, Hypoxia, and Metabolism
- CRISPR and Genetic Engineering
China Agricultural University
2025
Academy of Military Medical Sciences
2023-2025
University of Rhode Island
2016-2024
Institute of Microbiology
2023-2024
Anhui University of Finance and Economics
2023
Zhejiang University of Technology
2018-2020
Hangzhou Academy of Agricultural Sciences
2018
Massachusetts Institute of Technology
2010-2015
Center for Environmental Health
2010-2015
Beihang University
2012
The deoxycytidine analog KP1212, and its prodrug KP1461, are prototypes of a new class antiretroviral drugs designed to increase viral mutation rates, with the goal eventually causing collapse population. Here we present an extensive analysis sequences from HIV-1 infected volunteers first “mechanism validation” phase II clinical trial mutagenic base in which individuals previously treated antiviral received 1600 mg KP1461 twice per day for 124 days. Plasma loads were not reduced, overall...
Cancer-associated mutations often lead to perturbed cellular energy metabolism and accumulation of potentially harmful oncometabolites. One example is the chiral molecule 2-hydroxyglutarate (2HG); its two stereoisomers (d- l-2HG) have been found at abnormally high concentrations in tumors featuring anomalous metabolic pathways. 2HG has demonstrated competitively inhibit several α-ketoglutarate (αKG)- non-heme iron-dependent dioxygenases, including some AlkB family DNA repair enzymes, such as...
Significance Chronic inflammation is a significant risk factor for cancer and other human diseases. During chronic inflammation, cells exposed to neutrophil-derived hypochlorous acid accumulate in their genomes the DNA lesion 5-chlorocytosine (5ClC). Using battery of chemical, structural, genetic tools, present study demonstrates that 5ClC mutagenic lesion, suggesting genomic accumulation could have very serious biological consequences. induces C→T transitions, type mutation commonly...
5-Methylcytosine (5mC) in DNA CpG islands is an important epigenetic biomarker for mammalian gene regulation. It oxidized to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC) by the ten-eleven translocation (TET) family enzymes, which are α-ketoglutarate (α-KG)/Fe(II)-dependent dioxygenases. In this work, we demonstrate that marker 5mC modified 5hmC, 5fC, 5caC vitro another class of α-KG/Fe(II)-dependent proteins—the repair enzymes AlkB family, include...
Zika virus (ZIKV) infection during pregnancy threatens and fetal health. However, the infectivity pathological effects of ZIKV on placental trophoblast progenitor cells in early human embryos remain largely unknown. Here, using stem (hTSCs), we demonstrated that hTSCs were permissive to infection, resistance increased with hTSC differentiation. Combining gene knockout transcriptome analysis, intrinsic expression AXL TIM-1, absence potent interferon (IFN)-stimulated genes (ISGs) IFNs...
Abstract A mild and efficient protocol for visible‐light organoamine cocatalyzed difluoroalkylation of quinoxalin‐2(1 H )‐ones with functionalized difluoromethyl bromides has been developed. The transformation could be carried out at room temperature gave a variety C‐3 difluoroalkylated quinoxaline‐2(1 in moderate to excellent yields. Moreover, mechanistic studies revealed that this proceeded through radical‐type debrominative coupling process only need catalytic amount diisopropylethylamine...
Human β-defensin (HBD) has been recognized as a promising antimicrobial agent due to its broad-spectrum activity against various pathogens. In our previous work, we engineered chimeric human β-defensin, designated H4, by fusing 3 and 4, resulting in enhanced salt stability. However, the high cost of chemical synthesis relatively large number amino acids H4 limited applications. To reduce production costs, aimed develop an alternative method using prokaryotic expression system. We first...
The DNA and RNA repair protein AlkB removes alkyl groups from nucleic acids by a unique iron- α-ketoglutarate-dependent oxidation strategy. When alkylated adenines are used as targets, earlier work suggests that the initial target of can be carbon adjacent to N1. Such may case with ethano-adenine (EA), adduct formed an important anticancer drug, BCNU, whereby would occur at In previous study, several intermediates were observed suggesting pathway involving restructuring form not hinder...
Significance Unlike conventional antiviral therapy, lethal mutagenesis is a therapeutic strategy that exploits the high mutation rates of certain viruses. It works by intentionally increasing viral rate, causing excessive error accumulation and population collapse. The mutagenic nucleoside analog 5-aza-5,6-dihydro-2′-deoxycytidine (KP1212) specifically designed to use against HIV. mechanism KP1212 was proposed involve tautomerism—the repositioning active protons on nucleic acid base fast...
The AlkB protein is a repair enzyme that uses an α-ketoglutarate/Fe(II)-dependent mechanism to alkyl DNA adducts. has been reported highly susceptible substrates, such as 1-methyladenine and 3-methylcytosine, more efficiently in ss-DNA than ds-DNA. Here, we tested the of weaker substrates 1-methylguanine 3-methylthymine found prefers them We also discovered its human homologues, ABH2 ABH3, are able aforementioned adducts when adduct present mismatched base pair. These observations...
Abstract Etheno DNA adducts are a prevalent type of damage caused by vinyl chloride (VC) exposure and oxidative stress. mutagenic may contribute to the initiation several pathologies; thus, elucidating pathways which they induce cellular transformation is critical. Although N 2,3-ethenoguanine (N 2,3-εG) most abundant etheno adduct, its biological consequences have not been well characterized in cells due labile glycosidic bond. Here, stabilized 2′-fluoro-2′-deoxyribose analog 2,3-εG was...
A system consisting of a chiral lithium amide and n-BuLi in tol-d8 solution was investigated with 1H 13C INEPT DOSY, 6Li 15N NMR, other 2D NMR techniques. mixed 2:1 trimeric complex identified as the major species stoichiometry approached 1.5 equiv to 1 amine compound. DOSY spectra confirmed this aggregate solution. The formula weight aggregate, correlated diffusion coefficients internal references, indicated aggregation number complex. Plots log Drel vs FW are linear (r > 0.9900). titration...
A chiral enolate aggregate 1 containing a lithium and amide was systematically investigated by various NMR techniques. 1H 13C DOSY at 25 −78 °C provide its solution structure, aggregation number, formula weight. Multiple 2D 6Li techniques, such as 6Li−6Li EXSY, 6Li−1H HOESY, were utilized to investigate stereochemical structure. The configuration of the in complex confirmed HOESY trapping with TMS−Cl. unique coupling through Li−N−C−H network observed. This scalar corroborated HMQC, deuterium...
Structural diversification of canonical nucleic acid bases and nucleotide analogues by tautomerism has been proposed to be a powerful on/off switching mechanism allowing regulation many biological processes mediated RNA enzymes aptamers. Despite the suspected importance tautomerism, attempts observe minor tautomeric forms in or hybrid acid-ligand complexes have met with challenges due lack sensitive methods. Here, combination spectroscopic, biochemical, computational tools probed context an...
The dimeric structure is characterized for a chiral amide base complex consisting of an (S)-N-isopropyl-O-triisopropylsilyl valinol ligand and lithium. by variety NMR techniques, including multinuclear one- two-dimensional experiments diffusion-ordered spectroscopy (DOSY) as well diffusion coefficient-formula weight (D-fw) correlation analyses. Spartan calculations are presented which support the structural assignment. This characterization leads to explanation behavior reactivity these...
The AlkB enzyme is an Fe(II)- and α-ketoglutarate-dependent dioxygenase that repairs DNA alkyl lesions by a direct reversal of damage mechanism as part the adaptive response in E. coli. reported substrate scope includes simple adducts, such 1-methyladenine, 3-methylcytosine, 3-ethylcytosine, 1-methylguanine, 3-methylthymine, N6-methyladenine, well more complex 1,N6-ethenoadenine, 3,N4-ethenocytosine, 1,N6-ethanoadenine. Previous studies have revealed, piecemeal way, has impressive repertoire...
The structurally related exocyclic guanine adducts α-hydroxypropano-dG (α-OH-PdG), γ-hydroxypropano-dG (γ-OH-PdG), and M1dG are formed when DNA is exposed to the reactive aldehydes acrolein malondialdehyde (MDA). These lesions believed form basis for observed cytotoxicity mutagenicity of MDA. In an effort understand enzymatic pathways chemical mechanisms that involved in repair acrolein- MDA-induced damage, we investigated ability enzyme AlkB, α-ketoglutarate/Fe(II) dependent dioxygenase,...
Early diagnosis of Osteoarthritis (OA) is essential for preventing further cartilage destruction and decreasing severe complications. The aims this study are to explore the relationship between OA pathological grades quantitative acoustic parameters provide more objective criteria ultrasonic microscopic evaluation cartilage. Articular samples were prepared from rabbit knees scanned using ultrasound biomicroscopy (UBM). Three parameters, including roughness index surface (URI), reflection...
A copper salt-catalyzed cross-dehydrogenative coupling reaction between N-aryl glycine esters and acylated amines has been developed. The proceeded effectively under an oxygen atmosphere without the use of peroxide agents. This simple protocol allows for preparation a series new compounds in moderate to excellent yield via CDC wide range derivatives with amines, which are great interest field medicinal chemistry. plausible mechanism involving formation iminium ion intermediate, followed by...
Disturbed metabolism of copper ions can cause diseases such as Wilson's disease (WD). In this work, we investigated the inhibitory effect Cu(II) ion in vitro on AlkB family DNA repair enzymes, which are members Fe(II)/alpha-ketoglutarate-dependent dioxygenase and include human ALKBH2, ALKBH3, E. coli proteins. None three proteins was significantly inhibited under normal cellular concentrations. However, WD related condition, observed that activities all enzymes were strongly suppressed (from...