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The stimulator of interferon genes (STING) pathway is a potent therapeutic target for innate immunity. Despite the efforts to develop pocket‐dependent small‐molecule STING agonists that mimic the endogenous STING ligand, cyclic guanosine monophosphate–adenosine monophosphate (cGAMP), most of these agonists showed disappointing results in clinical t...
The stimulator of interferon genes (STING) pathway is a potent therapeutic target for innate immunity. Despite the efforts to develop pocket‐dependent small‐molecule STING agonists that mimic the endogenous STING ligand, cyclic guanosine monophosphate–adenosine monophosphate (cGAMP), most of these agonists showed disappointing results in clinical t...
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Immunostimulatory therapies based on pattern recognition receptors (PRRs) have emerged as an effective approach in the fight against cancer, with the ability to recruit tumor-specific lymphocytes in a low-immunogenicity tumor environment. The agonist cyclic dinucleotides (CDNs) of the stimulator of interferon gene (STING) are a group o...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with several antigenic variants, has grown into a global challenge, and the rapid establishment of an immune barrier is crucial to achieving long-term control of the virus. This has led to a great demand for easy preparation and scalable vaccines, especially in low-income countries. Here...
Protein posttranslational modifications (PTMs) are often involved in the mediation or inhibition of protein-protein interactions (PPIs) within many cellular signaling pathways. Uncovering the molecular mechanism of PTM-induced multivalent PPIs is vital to understand the regulatory factors to promote inhibitor development. Herein, Rnd3 peptides with...
A metal-free and base-free procedure for the phosphorylation of imidazo[1,2-a]pyridines with phosphine oxides under the irradiation of visible light at room temperature in green solvent was reported, featuring mild and sustainable conditions, convenient operation, as well as good functional group compatibility.
Constructing an effective therapeutic cancer vaccine is very attractive and promising for cancer immunotherapy. However, the poor immunogenicity of tumor antigens and suppression of the immune system in the tumor microenvironment are two major obstacles for developing effective cancer vaccines. Invariant NKT cells (iNKT cells), which are essential...
The association of K-Ras4B protein with plasma membrane (PM) is required for its signaling activity. Thus, direct inhibition of K-Ras4B-PM interaction could be a potential anti-Ras therapeutic strategy. However, it remains challenging to modulate such protein-PM interaction. Based on Ras isoform-specific PM microdomain localization patterns, we hav...
An efficient and practical one‐pot strategy for the synthesis of N‐sulfonylformamidines was developed by directly using easily available sulfonyl chlorides, sodium azide and tertiary/secondary amines in the presence of 5 mol‐% CuBr2 under aerobic oxidative conditions.
A novel and practical fluoroalkyl radical-initiated cascade reaction was developed to access diverse 2-fluoroalkylbenzothiazoles by reacting various fluoroalkyl radical sources, including perfluoroalkyl iodide (IC nF2 n+1, n = 3-8, 10), ICF(CF3)2, ICF2COOEt, ICF2CF2Cl, or ICF2CF2Br, tetramethylethane-1,2-diamine (TMEDA), and 2-isocyanoaryl thioethe...
The readily accessible and inexpensive dialkyl H -phosphonates are important building blocks for organic synthesis. This review specifically covers our recent work on the application of H -phosphonates as reactants for C–P bond formation, and as promoters for quinoline N -oxides to synthesize 2-functionalized quinolines.
TAR DNA binding protein 43 (TDP-43) is a key target in amyotrophic lateral sclerosis (ALS) treatment. Here, based on hydrophobic tagging strategy, we designed and synthesized a series of single or double hydrophobic tags conjugated peptides D1-D8. Among them, it was found that D4 displayed strongest ability to induce TDP-43 degradation in cells. D4...
Cyclic di-GMP (CDG) was applied to MUC1 glycopeptide-based cancer vaccines with physical mixing and built-in (at 2’-OH of CDG) strategies for activating STING pathway. CDG in two strategies both behaved...
Modulating the aggregation of Aβ has long been considered to be one of the potential methods to treat Alzheimer's disease (AD). It has been found that different Aβ species, including N‐terminal truncated or/and modified Aβ, co‐exist in the brain of AD patients. Yet there is currently little detailed work about the specific modulation of these Aβ sp...
Seryl-histidine dipeptide (Ser-His) has been recognized as the shortest peptide with hydrolysis cleavage activity; however, its protein cleavage spectrum has not yet been fully explored. Here, four differently folded proteins were treated with Ser-His, and the digestion products were evaluated with high-resolution mass spectrometry. The cleavage ef...
The selective killing of cancer cells and the avoidance of drug resistance are still difficult challenges in cancer therapy. Here, we report a new strategy that uses enzyme-induced gain of function (EIGF) to regulate the structure and function of phosphorylated melittin analogues (MelAs). Original MelAs have the capacity to disrupt plasma membranes...
Tau reduction is a favorable strategy for Alzheimer's disease (AD) treatment. In this work, we designed and synthesized a hydrophobic tag conjugated peptide (HyT-Tau-CPP) to selectively promote the degradation of Tau. HyT-Tau-CPP could potently lower the Tau level in a concentration- and time-dependent manner. Furthermore, HyT-Tau-CPP could also re...
Immunotherapy has become one of the most promising therapies for the treatment of diseases. Chemical molecule immunostimulants and nanomaterial immunostimulant systems are indispensable for the activation of the immune system in cancer immunotherapy. Here we report a strategy of self-assembled nano-immunostimulant (SANI) for synergistic immune acti...
Amyloid proteins are closely related with amyloid diseases and do tremendous harm to human health. However, there is still a lack of effective strategies to treat these amyloid diseases, so it is important to develop novel methods. Accelerating the clearance of amyloid proteins is a favorable method for amyloid disease treatment. Recently, chemical...
Cancer immunotherapy based on tumor vaccine is very promising and intriguing for carcinoma treatment. Herein, antitumor nanovaccines consisting of self-assembled chitosan (CS) nanoparticles and two-component mucin1 (MUC1) glycopeptide antigens were reported. Two different kinds of polyanionic electrolyte [sodium tripolyphosphate (TPP) and γ-poly-L-...
Two series of α-aminophosphonate derivatives containing a quinoline moiety have been designed and synthesized by introducing bioactive quinoline scaffold to α-aminophosphonate. The in vitro cytotoxic activities of target compounds were first investigated against two human cancer cell lines including Eca109 and Huh7 by MTT assay. Results revealed th...
Polymorphism of amyloid-β (Aβ) fibrils, implying different fibril structures, may play important pathological roles in Alzheimer's disease (AD). Morphologies of Aβ fibrils were found to be sensitive to fibrillation conditions. Herein, the Ser-8-phosphorylated Aβ (pAβ), which is assumed to specially associate with symptomatic AD, is reported to modi...
Synucleinopathies are a group of neurodegenerative diseases associated with alpha-synuclein (α-Syn) aggregation. Recently, increasing evidence has demonstrated the existence of different structural characteristics or ‘strains’ of α-Syn, supporting the concept that synucleinopathies share several common features with prion diseases and possibly expl...
Novel multi-component self-assembled nano-vaccines containing both Pam3CSK4 and CpG were developed for the first time. These multi-component vaccines could effectively activate the macrophages in vitro and elicit strong antibody immune responses and anti-tumor immune responses in vivo.
The Toll-like receptor 2 ligand Pam3CysSer is of particular interest for the construction synthetic vaccines owing to its stimulation of the innate immune system. Usually the vaccines comprise the Pam3CysSer with natural R configuration at the glycerol 2-position. Pam3CysSer peptide vaccines with natural configuration were shown to be more efficien...
Tau, an important pathological protein of Alzheimer's disease (AD), can mediate the toxicity of amyloid β (Aβ). Thus, reduction of Tau with chemical molecules may offer a novel strategy for treating AD. Here, we designed and synthesized a series of multifunctional molecules that contained Tau-recognition moieties and E3 ligase-binding moieties to e...
Antitumor vaccine, which is promising for tumor therapy, has been extensively studied. Some encouraging results of chemically synthetic vaccine designs based on the tumor-associated antigen mucin 1 have been achieved. However, some shortcomings such as low efficiency and difficult purification restrict their clinical application. To overcome these...
Two series of thieno[2,3-d]pyrimidine derivatives were designed and synthesized, in which bioactive α-aminophosphonate subunits were introduced at the N3 position through an N-N bond connection. The in vitro cytotoxic activity of the novel compounds was tested against human esophageal carcinoma cells (EC109), human hepatocarcinoma cells (HepG2), hu...
As mini-chemical models, amino acid ester isopropyl phosphoramidates of Brefeldin A (compounds 2a-2d) were synthesized and investigated by electrospray ionization tandem mass spectrometry in combination with H/D exchange. To further confirm the fragments's structures, off-line Fourier transform resonance tandem mass spectrometry (FT-ICR-MS/MS) was...
Promoting clearance of intracellular excessive tau is a potential therapeutic strategy for treating Alzheimer's disease. In this work, we designed and synthesized a cyclen-hybrid artificial ‘hydrolase’ I1-Cu(II) to cleave tau in vitro. Furthermore, a cell-permeable ‘hydrolase’ I2-Cu(II), derived from I1-Cu(II), was also synthesized to cleave intrac...
A new fluorescent "on-off' chemosensor for Hg2+ initiated by a derivative of rhodamine B was designed and synthesized. Compound 1 exhibited high sensitivity and selectivity for Hg2+ over other commonly coexistent metal ions in aqueous media. Upon the addition of Hg2+, the spirocyclic ring of probe is opened and a significant enhancement of visible...
C53H51IrN4O2, triclinic, P (1) over bar (no. 2), a = 11.0757(9) angstrom, h= 13.423(1) angstrom, c= 17.156(2) angstrom, alpha = 90.282(1)degrees, beta = 105.346(1)degrees, gamma = 112.146(1)degrees, V=2262.5 angstrom(3), Z= 2, R-gt(F) = 0.041, wR(ref)(F-2) = 0.090, T = 296 K.
C16H14N2, monoclinic, P121/c1 (no. 14), a = 8.387(1) Å, b = 17.453(3) Å, c = 8.694(1) Å, β = 93.092(2)°, V= 1270.8 Å3, Z = 4, Rgt(F) = 0.046, wRref(F2) = 0.129, T=294 K.
Multivalent synthetic vaccines were obtained by solid-phase synthesis of tumor-associated MUC1 glycopeptide antigens and their coupling to a Pam3 Cys lipopeptide through click reactions. These vaccines elicited immune responses in mice without the use of any external adjuvant. The vaccine containing four copies of a MUC1 sialyl-TN antigen showed a...
The T-helper epitope peptide P30 (green in the scheme) from tetanus toxoid was used as the immunostimulant in MUC1 glycopeptide antitumor vaccines and apparently also acts as a built-in adjuvant. P30-conjugated glycopeptide vaccines containing three glycans in the immunodominant motifs PDTRP and GSTAP induced much stronger immune responses and comp...
HIV entry is mediated by the envelope glycoproteins gp120 and gp41. The gp41 subunit contains several functional domains: the N-terminal heptad repeat (NHR) domains fold a triple stranded coiled-coil forming a meta-stable prefusion intermediate. C-terminal heptad repeat (CHR) subsequently folds onto the hydrophobic grooves of the NHR coiled-coil to...
Glycopeptides of tumor-associated mucin MUC1 are promising target structures for the development of antitumor vaccines. Because these endogenous structures were weakly immunogenic, they were coupled to immune-response-stimulating T-cell epitopes and the Pam(3) Cys lipopeptide to induce strong immune responses in mice. A new thioether-ligation metho...
A novel compound 1 containing rhodamine B and macrocyclic groups has been synthesized. It was found to exhibit a reversible colorimetric response, high selectivity and sensitivity for Cu(II) ion over other commonly coexistent metal ions. The colorimetric and fluorescent response to Cu(II) can be conveniently detected even by the naked eye, which pr...
The differences in the C-terminal domains of human amylin peptide variants initiate different aggregation processes and differences in the composition of the aggregates by affecting the hydrophobic cores, conformations, and intra-sheet interactions of the peptides, which have distinct effects on the cytotoxicity of the peptides.
In this paper, we describe the development of a novel stable-isotope N-phosphorylation labeling (SIPL) strategy for peptide de novo sequencing and protein quantification base on organic phosphorus chemistry. The labeling reaction could be performed easily and completed within 40 min in a one-pot reaction without additional cleanup procedures. Diffe...
Lys16 is present in the core region of the amyloid β (Aβ) self-assembly in Alzheimer's disease. Here we report that the P9-NCS peptide can covalently react with Lys16 and inhibit Aβ neurotoxic fibrillization. Moreover P9-NCS has high selectivity and it cannot react with amylin, insulin, fetal bovine serum, Q11 and MUC1 peptide.
Insulin assembly follows different pathways under different environments. But the mechanism of insulin assembly and the pathology of insulin-related amyloidosis diseases remain unclear. This work, illustrating different pathways of insulin aggregation induced by short peptide segment, may shed light on these research areas. We find that the short p...
The separation of d4T-P-N-PheOMe diastereoisomers has been carried out by supercritical fluid chromatography on Hypersil ODS2 column (250 mm × 4.6 mm, 5 μm). Supercritical CO2 modified with methanol, ethanol and 2-propanol were used as mobile phase. The influence of type and concentration of alcohol modifier, back pressure and column temperature on...
HIV entry is mediated by the envelope glycoproteins gp120 and gp41. The gp41 subunit contains several functional domains: the N-terminal heptad repeat (NHR) domains fold a triple stranded coiled-coil forming a meta-stable prefusion intermediate. The C-terminal heptad repeat (CHR) subsequently folds onto the hydrophobic grooves of the NHR coiled-coi...
Human islet amyloid polypeptide (hIAPP) shows an antimicrobial activity towards two types of clinically relevant bacteria. The potency of hIAPP varies with its aggregation states. Circular dichroism was employed to determine the interaction between hIAPP and bacteria lipid membrane mimic. The antimicrobial activity of each aggregate species is asso...
In the development of vaccines for epithelial tumors, the key targets are MUC1 proteins, which have a variable number of tandem repeats (VNTR) bearing tumor-associated carbohydrate antigens (TACAs), such as Tn and STn. A major obstacle in vaccine development is the low immunogenicity of the short MUC1 peptide. To overcome this obstacle, we designed...
A shot in the arm for anticancer vaccines: Synthetic MUC1 glycopeptides bearing the STn and 2,6-ST antigens were conjugated covalently to BSA. The obtained synthetic vaccines induced very strong immune responses in Balb/c mice. Predominant IgG isotype antibodies were induced. The antibodies exhibited strong binding to breast cancer cells of the MCF...
Two rhodamine-based fluorescent probes were synthesized, and their sensing behavior toward metal ions was investigated by fluorescence spectroscopy. Small structural modifications (tuning) of the compounds afforded enhanced fluorescence in the presence of Cr(III) and Pb(II) in CH3CN solution, whereas other ions including Zn(II), Ni(II), Hg(II), Cd(...
A new bis(rhodamine)-based fluorescent probe 4 was synthesized, and it exhibited high selectivity for Fe3+ over other commonly coexistent metal ions in both 50% ethanol and Tris–HCl buffer. Upon the addition of Fe3+, the spirocyclic ring of 4 was opened and a significant enhancement of visible color and fluorescence in the range of 500–600 nm was o...
Copper is known to be a critical factor in Alzheimer's disease (AD) pathogenesis, as it is involved in amyloid-β (Aβ) peptide related toxicity. However, the relationship between neurotoxicity and Aβ peptide in the presence of copper remains unclear. The effect of copper has not been clearly differentiated between Aβ42 and Aβ40, and it is still deba...
The membrane-bound tumor-associated glycoprotein MUC1 is aberrantly glycosylated in cancer cells compared with normal cells, and is therefore considered an attractive target for cancer immunotherapy. However, tumor-associated glycopeptides from MUC1 do not elicit a sufficiently robust immune response. Therefore, antitumor vaccines were developed, w...
The non-covalent interaction between a series of N-phosphoryl dipeptides (or methyl esters) (DPP) and protein was studied by ESI-MS and UV–vis spectrometer. The function of
different groups in DPP and binding sites of protein were investigated. The results revealed that hydroxyl and aromatic ring
in DPP were both important group for the interaction...
Blocking the interaction between the E4 isoform of apolipoprotein E (ApoE) and amyloid beta-peptide (Aβ) may be an avenue for pharmacological intervention in Alzheimer's disease (AD). The main regions of interaction of the two proteins are, respectively, ApoE244-272 and Aβ12-28. These protein segments are too large to facilitate the design of small...
Shikonin (β-alkannin), a naphthazarin derivative, has shown a variety of abilities such as anti-inflammatory, antitumoral, cytotoxic, and antimicrobial activities. In the presence of Cu(II), shikonin caused breakage of supercoiled plasmid pBR322 DNA. Other metal ions tested [Mg(II), Ca(II), and Ni(II)] were ineffective and only Fe(II) has the same...
There are two independent molecules in the asymmetric unit of the title compound, C19H33N2O4P. In the crystal, the two independent molecules are linked via N—H⋯O=P hydrogen bonds, forming dimers.
Three ligands which contain histidine and conjugated by a flexible linker, have been characterized and evaluated as DNA cleavage
agents. The cleavage activity of metal complexes were evaluated by monitoring the conversion of supercoiled plasmid DNA (pUC19)
(Form I) to nicked circular DNA (Form II) by agarose gel electrophoresis. The results showed...
Amino acid thiophosphoramidates of nucleoside were synthesized and determined by negative ion electrospray ionization mass spectrometry (ESI-MS) in conjunction with tandem mass spectrometry (MS/MS). Hie fragmentation pathways were investigated. The results show that ESI-MS is a useful tool for structural determination of amino acid thiophosphoramid...
A new family of artificial transcription factor (ATF)-based conjugates have been designed and synthesized as potent chemical nucleases. Polyamides as the important and efficient ATFs were used to modify and activate several anchor compounds. The results demonstrate that the resulting conjugates remarkably promote the rate accelerations and non-rand...
Human islet amyloid polypeptide (hIAPP) deposit is the hallmark of type 2 diabetes pathology. Here, we report that apo-cyclen, attached to a specific hIAPP recognition motif (NYGAIL), captured copper ions and became proteolytically active. This cyclen-NYGAIL-copper complex was able to interfere with hIAPP aggregation and cleave hIAPP. These activit...
Copper enhances amyloid cytotoxicity and mediates human islet amyloid polypeptide (hIAPP) oligomerization; nickel, a redox inactive metal with similar protein binding affinity to copper, also mimics this effect, thereby demonstrating copper-mediated hIAPP cytotoxicity is due mainly to granular oligomer generation rather than ROS accumulation in typ...
For Abstract see ChemInform Abstract in Full Text.
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
A new method is introduced by thermolysis of 5′-O-trityl-2′,3′-O-triphenylphosphoranediyluridine [4]4.
Chang , B. C. ,
Conrad , W. E. ,
Denney , D. B. ,
Denney , D. Z. ,
Edelman , R. ,
Powell , R. L. and
White , D. W. 1971. J. Am. Chem. Soc., 93: 4004–4009. View all references with or without the presence of methanol to afford the 3-N-methyl...
Amyloid-beta (Abeta) aggregation and Cu(II)-related oxidative stress are involved in the dysfunction and death of neurons in Alzheimer's disease (AD). However, the relationship between Abeta and Cu(II) is not clear. Furthermore, the pro- or anti-oxidant properties of Abeta are also under great debate. Here the H2O2 generating ability of Abeta42 in...
The interactions between ATP and N-(O,O-diisopropyl) phosphoryl-L-alanine (DIPP-Ala), N-(tert-butoxycarbonyl)-L-alanine (Boc-Ala), or L-alanine (Ala) were investigated by electrospray ionization tandem mass spectrometry (ESI-MS/MS). The non-covalent complexes between ATP and Boc-Ala or DIPP-Ala were observed, while the complex between ATP and Ala w...
Phosphorylation has to have been one of the key events in prebiotic evolution on earth. In this article, the emergence of phosphoryl amino acid 5′-nucleosides having a P–N bond is described as a model of the origin of amino acid homochirality and Genetic Code. It is proposed that the intramolecular interaction between the nucleotide base and the am...
The binary mixtures of 7 hexoses and 20 amino acids were investigated by electrospray ionization ion trap mass spectrometry (ESI-ITMS). The adduct ions of the amino acid and the hexose were detected for 12 amino acids but not for the other 8 amino acids which are basic acidic amino acids and amides. The ions of amino acid-hexose complexes were furt...
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Electrospray ionization mass spectrometry (ESI-MS) is a powerful method for sequencing peptides. A novel fragmentation pattern with the loss of a neutral fragment of 45 Da was observed with the dipeptides, tripeptides, tetrapeptides and pentapeptides containing phenylalanine or histidine residues. A novel rearrangement reaction with the extrusion o...
Novel alkyl thiophosphoramidate derivatives of nucleoside analogues (5) have been prepared by phosphochloridothioate chemistry. O-Isopropyl 2′, 3′-O-isopropylidene uridine-5′-yl N-thiophosphoryl threonine and serine methyl esters (Sa and 5b) underwent the intramolecular catalyzed hydrolysis reaction.
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
A convenient, efficient and general method has been developed for synthesis of H-phosphonate mono and diesters of AZT and d4T through one-pot reaction of phosphonic acid with AZT or d4T and different alcohols using pivaloyl chloride as condensing agent under mild conditions.