A5026104904- Bladder and Urothelial Cancer Treatments
- Urinary and Genital Oncology Studies
- Supramolecular Self-Assembly in Materials
- Peptidase Inhibition and Analysis
- Prostate Cancer Treatment and Research
- Prostate Cancer Diagnosis and Treatment
- Advanced biosensing and bioanalysis techniques
- RNA Interference and Gene Delivery
- Monoclonal and Polyclonal Antibodies Research
- Chemical Synthesis and Analysis
- Polydiacetylene-based materials and applications
- Nanoplatforms for cancer theranostics
- Glycosylation and Glycoproteins Research
- Ubiquitin and proteasome pathways
- Bacteriophages and microbial interactions
- Supramolecular Chemistry and Complexes
- Antimicrobial Peptides and Activities
- Lipid Membrane Structure and Behavior
- SARS-CoV-2 and COVID-19 Research
- Biosensors and Analytical Detection
- Radiopharmaceutical Chemistry and Applications
- RNA and protein synthesis mechanisms
- MRI in cancer diagnosis
- Cancer-related molecular mechanisms research
- Carbon and Quantum Dots Applications
Peking University
2025
Kunming Medical University
2025
Peking University Cancer Hospital
2025
University of California, San Francisco
2020-2024
Zhejiang Chinese Medical University
2024
Chinese University of Hong Kong
2024
University of Hong Kong
2024
Hebei General Hospital
2022-2023
North China University of Science and Technology
2022-2023
Third Affiliated Hospital of Guangzhou Medical University
2022
d-Peptides, as the enantiomers of naturally occurring l-peptides, usually resist endogenous proteases and are presumably insensitive to most enzymes. But, it is unclear whether or how a phosphatase catalyzes dephosphorylation from d-peptides. In this work, we examine formation nanofibers d-peptides via enzymatic dephosphorylation. By comparing hydrogelation l-peptide d-peptide based hydrogelators, find that chirality precursors hydrogelators affects little on resulted removal phosphate group...
Selective inhibition of cancer cells remains a challenge in chemotherapy. Here we report the molecular and cellular validation enzyme-instructed self-assembly (EISA) as multiple step process for selectively killing that overexpress alkaline phosphatases (ALPs). We design synthesize two kinds d-tetrapeptide containing one or phosphotyrosine residues with N-terminal capped by naphthyl group. Upon enzymatic dephosphorylation, these d-tetrapeptides turn into self-assembling molecules to form...
Abstract Anticancer drug resistance demands innovative approaches that boost the activity of drugs against drug‐resistant cancers without increasing systemic toxicity. Here we show use enzyme‐instructed self‐assembly (EISA) to generate intracellular supramolecular assemblies drastically cisplatin ovarian cancer cells. We design and synthesize small peptide precursors as substrates carboxylesterase (CES). CES cleaves ester bond pre‐installed on form peptides self‐assemble in water nanofibers....
Due to their biostability, d-peptides are emerging as an important molecular platform for biomedical applications. Being proteolytically resistant, lack interactions with endogenous transporters and hardly enter cells. Here we show that taurine, a natural amino acid, drastically boosts the cellular uptake of small in mammalian cells by >10-fold, from 118 μM (without conjugating taurine) >1.6 mM (after taurine). The large amount ester conjugate taurine d-peptide allows intracellular esterase...
Anisotropy or alignment is a critical feature of functional soft materials in living organisms, but it remains challenge for spontaneously generating anisotropic gel materials. Here we report molecular design that increases intermolecular aromatic-aromatic interactions hydrogelators during enzymatic hydrogelation forming an hydrogel. This process, relying on both and enzyme catalysis, results aligned supramolecular nanofibers as the matrices monodomain hydrogel exhibits significant...
Self-assembling dipeptides conjugated to naphthalene show considerable promise as nanomaterial structures, biomaterials, and drug delivery devices. Biomaterial infections are responsible for high rates of patient mortality morbidity. The presence biofilm bacteria, which thrive on implant surfaces, a huge burden healthcare budgets, they highly resistant current therapeutic strategies. Ultrashort cationic self-assembled peptides represent innovative cost-effective strategy form antibacterial...
Peptides made of D-amino acids, as the enantiomer corresponding L-peptides, are able to resist proteolysis. It is, however, unclear or much less explored whether how acids affect cellular response supramolecular nanofibers formed by enzyme-triggered self-assembly D-peptides. In this work, we choose a cell compatible molecule, Nap-L-Phe-L-Phe-L-(p)Tyr (LLL-1P), and systematically replace L-amino in tripeptidic precursor its hydrogelator acid(s). The replacement even one acid increases...
We report that phosphotyrosine–cholesterol conjugates effectively and selectively kill cancer cells, including platinum-resistant ovarian cells. The conjugate increases the degree of noncovalent oligomerization upon enzymatic dephosphorylation in aqueous buffer. This conversion also results assembly cholesterol inside outside cells leads to cell death. Preliminary mechanistic studies suggest formed assemblies not only interact with actin filaments microtubules but affect lipid rafts. As...
Abstract The increase of bacterial resistance demands rapid and accurate diagnosis infections. Biosurface‐induced supramolecular assembly for therapy has received little attention in detecting Herein we present a dual fluorescent‐nuclear probe based on self‐assembly vancomycin (Van) Gram‐positive bacteria imaging infection. A Van‐ rhodamine‐modified peptide derivative (Rho‐FF‐Van), as the agent, binds to terminal methicillin‐resistant staphylococcus aureus (MRSA) self‐assembles form...
The color of gold: Bacterial β-lactamases (Blas) can be rapidly identified by a simple and specific colorimetric assay with gold nanoparticles (Au-NPs). This evaluate enzymatic kinetic reactions screen inhibitors Blas in real time, offers economical method for the rapid detection β-lactam resistant bacteria clinical studies. Supporting information this article is available on WWW under http://www.wiley-vch.de/contents/jc_2002/2007/z702773_s.pdf or from author. Please note: publisher not...
Besides tight and specific ligand-receptor interactions, the rate regulation of formation molecular assemblies is one fundamental features cells. But latter receives little exploration for developing anticancer therapeutics. Here we show that a simple design substrates phosphatases-tailoring number phosphates on peptidic substrates-is able to regulate self-assembly enzyme reaction product. Such allows selective inhibition osteosarcoma cells over hepatocytes, which promises target cancer in...
Abstract As a new class of biomaterials, most supramolecular hydrogels formed by small peptides require the attachment long alkyl chains, multiple aromatic groups, or strong electrostatic interactions. Based on fact that abundant protein assemblies in nature are dimeric, we select short peptide sequences from interface heterodimer proteins with known crystal structure to conjugate nucleobases form nucleopeptides. Being driven mainly hydrogen bonds, nucleopeptides self‐assemble nanofibers,...
As a promising molecular process for selectively inhibiting cancer cells without inducing acquired drug resistance, enzyme-instructed self-assembly (EISA) usually requires relatively high dosages. Despite its discovery 30 years ago, the translation of knowledge about NF-κB signaling into clinic remains complicated due to broad roles in cellular regulation. Here we show that integrating EISA and targeting boosts efficacy over an order magnitude compromising selectivity against cells. That is,...
Tight ligand‐receptor binding, paradoxically, is a major root of drug resistance in cancer chemotherapy. To address this problem, instead using conventional inhibitors or ligands, paper focuses on the development novel process—enzyme‐instructed self‐assembly (EISA)—to kill cells selectively. Here it demonstrated that EISA as an intracellular process to generate nanofibrils short peptides for selectively inhibiting cell proliferation, including resistant ones. As turns non‐self‐assembling...
Extracellular proteolysis is frequently dysregulated in disease and can generate proteoforms with unique neoepitopes not found healthy tissue. Here, we demonstrate that Abs selectively recognize a proteolytic neoepitope on CUB domain containing protein 1 (CDCP1) could enable more effective safer treatments for solid tumors. CDCP1 highly overexpressed RAS-driven cancers, its ectodomain cleaved by extracellular proteases. Biochemical, biophysical, structural characterization revealed the 2...
Here we report supramolecular hydrogelators made of nonsteroidal anti-inflammatory drugs (NSAID) and small peptides. The covalent linkage Phe-Phe NSAIDs results in conjugates that self-assemble water to form molecular nanofibers as the matrices hydrogels. When NSAID is naproxen (1), resultant hydrogelator 1a forms a hydrogel at critical concentration (cgc) 0.2 wt % pH 7.0. Hydrogelator 1a, also acting general motif, enables enzymatic hydrogelation which precursor turns into upon hydrolysis...
Significance Over 600 proteases work together to maintain the normal functions and homeostasis of cells in human body. Determining protease specificity their natural substrates is critical understanding biology. We present a facile, inexpensive, general, global means profile at unprecedented depth. Using two genetically encoded substrate phage libraries, we deeply specificities important families, caspases involved cell death ADAMs family that shed membrane proteins. validated our results by...
Because they exhibit important biological functions, from unfolding proteins to activating enzymes controlling cell fates, aggregates of small molecules are able serve as functional molecular entities in cellular environments. However, the inability precisely control their production has hampered understanding and exploration functions. Here we show that well-established ligand–receptor interaction between vancomycin d-Ala-d-Ala catalyzes aggregation a d-Ala-d-Ala-containing peptide...