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Publications (80)
The regeneration of demineralized enamel holds great significance for the treatment of dental caries. Amelogenin (Ame), an essential protein for mediating natural enamel growth, is no longer secreted after enamel...
The biogenesis of exosomes that mediate cell‐to‐cell communication by transporting numerous biomolecules to neighbouring cells is an essential cellular process. The interaction between the transmembrane protein syndecan‐4 (SDC4) and cytosolic protein syntenin plays a key role in the biogenesis of exosomes. However, how the relatively weak binding o...
Prenylated proteins contain C15 or C20 isoprenoids linked to cysteine residues positioned near their C-termini. Here we describe the preparation of isoprenoid diphosphate analogues incorporating diazirine groups that can be used to probe interactions between prenylated proteins and other proteins that interact with them. Studies using synthetic pep...
Tau plays a major role in Alzheimer's disease (AD) and several other neurodegenerative diseases. Tau undergoing liquid-liquid phase separation (LLPS) performs specific physiological functions, induces pathological processes, and contributes to neurodegeneration. Regulating Tau phase separation helps maintain physiological functions of Tau and inhib...
Phosphine ligands are the most important class of ligands for cross-coupling reactions due to their unique electronic and steric properties. However, metalloproteins generally rely on nitrogen, sulfur, or oxygen ligands. Here, we report the genetic incorporation of P3BF, which contains a biocompatible borane-protected phosphine, into proteins. This...
Mitigation of biofouling and the host's foreign body response (FBR) is a critical challenge with biomedical implants. The surface coating with various anti-fouling materials provides a solution to overcome it, but limited options in clinic and their potential immunogenicity drive the development of more alternative coating materials. Herein, inspir...
Polypeptides, a kind of very promising biomaterial, have shown a wide range of applications due to their excellent biocompatibility, easy accessibility, and structural variability. To synthesize polypeptides with desired functions, post‐polymerization modification (PPM) plays an important role in introducing novel chemical structure on their side‐c...
Biomimetic mineralization based on self-assembly has made great progress, providing bottom-up strategies for the construction of new organic–inorganic hybrid materials applied in the treatment of hard tissue defects. Herein, inspired by the cooperative effects of key components in biomineralization microenvironments, a new type of biocompatible pep...
Gao Li Jun Hu Huai Chen- [...]
Yan-Mei Li
Utilizing the interactions between tryptophan, methyl viologen and cucurbit[8]uril, we found that the distance between the targeted peptides/protein and the reactive peptide was shortened, which facilitated the Michael addition reaction...
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 novel STING agonist, CDGSF, ipsilaterally modified with phosphorothioate and fluorine, was synthesized. The phosphorothioate in CDGSF might be a site for covalent conjugation. Injection of CDGSF generated an immunogenic (“hot”) tumor microenvironment to suppress melanoma, more efficiently than dithio CDG. In particular, immunization with SARS-CoV...
We developed a new responsive peptide hydrogel FmocFFpSC(oNB)-PEG, which could achieve gel formation induced by calcium ions and sequential dissolution stimulated by light. It provides a potential delivery system for...
A novel STING agonist CDGSF unilaterally modified with phosphorothioate and fluorine was synthesized. CDGSF displayed better STING activity over dithio CDG. Immunization of SARS-CoV-2 Spike protein with CDGSF as an adjuvant elicited an exceptional high antibody titer and a robust T cell response, which were better than the group using aluminium hyd...
We developed a host−guest ATP responsive strategy for efficient intracellular delivery of phosphopeptides, employing pegylated arginine clustered calix[5]arene nanocarrier system that had great capabilities of recoginizing the phosphate moities on...
Herein, we successfully semi-synthesized TDP-43 prion-like domain with Ser404 phosphorylation. We demonstrated that Ser404 phosphorylation could accelerate the amyloid aggregation of TDP-43 prion-like domain and aggravate its cytotoxicity.
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...
We report a facile synthetic strategy toward CH2-substituted phosphothreonine mimetic. Herein, inexpensive valine with directing group was converted into homothreonine via palladium-catalyzed γ-methyl C(sp³)-H bond activation, followed by construction of phosphorus-carbon bond via well-developed Appel reaction and Michaelis-Becker reaction with a t...
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...
Intracellular protein delivery is of significance for cellular protein analysis and therapeutic development, but remains challenging technically. Herein, we report a general and highly potent strategy for intracellular protein delivery based on commercially available cationic lipids. In this strategy, a designed double branching poly-glutamate tag...
A novel and facile synthetic strategy for α,α-difluorinated phosphonate mimetics of phosphoserine/phosphothreonine utilizing rhodium-catalyzed asymmetric hydrogenation was developed. The dehydrogenated substrate β-difluorophosphonomethyl α-(acylamino)acrylates were first prepared from protected serine/threonine followed by asymmetric hydrogenation...
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...
Phosphatase-inert peptidomimetics containing phosphonate pSer analogue have been developed as valuable biological tools for probing and regulating pSer-dependent protein-protein interactions (PPIs) in cellular context. Herein, we report a facile and efficient synthesis route of Fmoc-protected phosphonate pSer mimetic and also present the applicatio...
K-Ras4B is one of the most frequently mutated Ras isoforms in cancers. The signaling activity of K-Ras4B depends on its localization to the plasma membrane (PM), which is mainly mediated by its polybasic farnesylated C-terminus. On top of the constitutive cycles that maintain the PM enrichment of K-Ras4B, conditional phosphorylation at Ser181 locat...
Helical intermediates play important roles in the aggregation process of amyloid proteins. Herein, constrained helices were synthesized to mimic different helical structures reported in Aβ and the different modulation effects on Aβ aggregation were verified. Especially, Aβ (17-23) stabilized in helical conformation would definitely transform Aβ agg...
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-...
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...
Clearance of Aβ by immunotherapy is one of the fancy methods to treat Alzheimer’s disease (AD). However, the failure of some clinical trials suggested that there may be something ignored in the past development of immunotherapy. Pyrogluta-mate-3 Aβ (AβpE3-X), which was found to be abundant in the patients’ brain, has attracted much attention after...
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...
A site-specific dual-color labeled ubiquitin for sensing deubiquitinase's activity was prepared by consecutively using chemoselective native chemical ligation reactions in a facile and efficient way. The prepared sensor was applied to establish a sensitive FRET-based assay for UCH-L3.
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...
A new type of -NH- bridged azacalix[2]arene[2]carbazoles has been synthesized by aromatic nucleophilic substitution reaction via one pot and/or fragment coupling strategy. Both symmetric and unsymmetric macrocycles are obtained. X-ray single crystal analysis reveals 1, 3-alternation conformation of the macrocycle. The spectroscopic and electrochemi...
TEV protease is of great importance for in vitro and in vivo site-specific cleavage of proteins. The proteolytic efficiency of TEV protease is often regulated by mutation of the substrate, which is irreversible and hard to be modulated. Herein, a facile and reversible method, based on phosphorylation in the substrate, is developed to regulate the c...
Introduction:
Current evidence suggests potential efficacy of cognitive behavioral therapy for insomnia (CBT-I) in older adults. Mobile applications (apps) have been developed to facilitate CBT-I in the general population. However, because of deteriorating perceptual and cognitive functioning, the effectiveness of mobile apps in older adults remai...
Synthetic tumor vaccines have been proven to be promising for cancer immunotherapy. However, the limitation of the specificity and efficiency of the synthetic tumor vaccines need further improvements. To overcome these difficulties, additional tumor-associated targets need to be identified, and optimized structural designs of vaccines need to be el...
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...
Alzheimer’s disease (AD) is one of the most common types of dementia whose hallmarks include neurofibrillary tangles and senile plaques. The latter are mainly composed of amyloid-β proteins (Aβ), and it’s suggested that Aβ may be the causative factor in AD pathogenesis. Immunotherapy targeting Aβ for preventing aggregation of Aβ and mildly clearing...
Developing compounds regulating amyloid toxic oligomer but not fibril formation should constitute an effective strategy for the treatment of diabetes. Based on the full understanding of the folding mechanism, we designed an orthosteric helix regulator that can promote hIAPP to assemble into large non-cytotoxic oligomers. As a result, the islet cell...
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...
Reducing the negative effects of extended computer use is becoming increasingly important and it has been demonstrated that appropriate stretching yields benefits. We investigated the opportunities of motivating heavy computer users to stretch by incorporating mobile and sensing technologies into a 1-on-1 social competition game. We implemented the...
Neurofibrillary tangles composed of tau protein and senile plaque accumulated by amyloid-β (Aβ) are two hallmarks in Alzheimer disease (AD). In the patients with AD, tau is abnormally hyperphosphorylated, mutated or misfolding, which endows tau with stronger tendency to aggregate. Tau protein has the potency to mediate neuron toxicity of Aβ. The re...
Cognitive behavioral therapy for insomnia (CBT-I) is a treatment that focuses on psychological and behavioral factors. Although the CBT-I has proven efficacy, yet 32%-V89% of patients fail to consistently follow recommendations. The critical challenge of CBT-I is how to enhance the adherence of patients to therapy. In this study, we propose a persu...
Defects in primary cilia result in human diseases known as ciliopathies. The retinitis pigmentosa GTPase regulator (RPGR), mutated in the most severe form of the eye disease, is located at the transition zone of the ciliary organelle. The RPGR-interacting partner PDEδ is involved in trafficking of farnesylated ciliary cargo, but the significance of...
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...
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.
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.
Access to the ciliary membrane for trans-membrane or membrane-associated proteins is a regulated process. Previously, we have shown that the closely homologous small G proteins Arl2 and Arl3 allosterically regulate prenylated cargo release from PDEδ. UNC119/HRG4 is responsible for ciliary delivery of myristoylated cargo. Here, we show that although...
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...
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...
Lipidated Rho and Rab GTP-binding proteins are transported between membranes in complex with solubilizing factors called 'guanine nucleotide dissociation inhibitors' (GDIs). Unloading from GDIs using GDI displacement factors (GDFs) has been proposed but remains mechanistically elusive. PDEδ is a putative solubilizing factor for several prenylated R...
Understanding protein structure and function is essential for uncovering the secrets of biology, but it remains extremely challenging because of the high complexity of protein networks and their wiring. The daunting task of elucidating these interconnections requires the concerted application of methods emerging from different disciplines. Chemical...
Now available! Farnesylated and carboxymethylated Rheb (see picture) and K-Ras4B GTPases were synthesized in useful amounts by a combination of expressed protein ligation and solid-phase lipopeptide synthesis. The functionality of the proteins was proven by biochemical, biophysical, and cell-based investigations.
中文词汇网络(Chinese WordNet, 简称CWN) 的设计理念, 是在完整的知识系统下兼顾词义与
词义关系的精确表达与语言科技应用. 中文词义的区分与词义间关系的精确表征必须建立在语言
学理论, 特别是词汇语义学的基础上. 而词义内容与词义关系的发掘与验证,
则必须源自实际语料. 我们采用的方法是分析与语料结合. 结合的方式则除了验证与举例外,
主要是在大量语料上平行进行词义标记, 以反向回馈验证. 完整, 强健知识系统的建立,
是兼顾知识本体(ontology) 的完备规范(formal integrity) 和人类语言系统内部的完整知识.
A facile synthesis of cyclopeptide-centered multivalent glycoclusters using Cu(I) catalyzed Huisgen 1,3-dipolar cycloaddition of azides and terminal alkynes, so called 'click chemistry', has been developed. The affinities of mannose-specific protein Concanavalin A (Con A) toward two synthetic glycoclusters respectively bearing divalent or tetravale...
A pentasaccharide mimic of a fragment of the capsular polysaccharide of Streptococcus pneumoniae type 15C beta-D-Galp-(1-->4)-beta-D-Glcp-(1-->6)-[alpha-D-Galp-(1-->2)-beta-D-Galp-(1-->4)]-beta-D-GlcpNAc-(1-->OCH2CH2N3) (1) was synthesized in a regio- and stereoselective manner. The 2-azidoethyl-spacered pentasaccharide mimic 1 can be used to const...
Serine and threonine residues in many proteins can be modified by either phosphorylation or GlcNAcylation. To investigate the mechanism of O-GlcNAc and O-phosphate's reciprocal roles in modulating the degradation and activity of murine estrogen receptor beta (mER-beta), the conformational changes induced by O-GlcNAcylation and O-phosphorylation of...
Nuclear import triggered by the nuclear-localisation sequence (NLS) of the viral Jun (vJun) protein is mediated by phosphorylation of a serine close to the NLS. Since phosphorylation and glycosylation of serine residues are often in a reciprocal "yin-yang" relationship, we investigated whether glycosylation of this serine with O-linked N-acetylgluc...
A sense-based lexical knowledgebase is a core foundation for language engineering. Two important criteria must be satisfied when constructing a knowledgebase: linguistic felicity and data cohesion. In this paper, we discuss how data cohesion of the sense information collected using the Sinica Sense Management System (SSMS) can be achieved. SSMS man...