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On-Demand Drug Release from Click-Refillable Drug Depots.

Stimuli-responsive, on-demand release of drugs from drug-eluting depots could transform the treatment of many local diseases, providing intricate control over local dosing. However, conventional on-demand drug release approaches rely on locally implanted drug depots, which become spent over time and cannot be refilled or reused without invasive procedures. New strategies to noninvasively refill drug-eluting depots followed by on-demand release could transform clinical therapy. Here we report an on-demand drug delivery paradigm that combines bioorthogonal click chemistry to locally enrich proto…

Ice Confinement Enabled Click Conjugation of DNA Oligonucleotides and Macromolecules.

DNA bioconjugates integrate the programmable recognition and structural precision of nucleic acids with the diverse properties of (bio)polymers, enabling functional architectures across sensing, biomedicine, and nanotechnology. While versatile conjugation chemistry (e.g., click reaction) is available, linking DNA oligonucleotides with synthetic polymers and biomacromolecules is hampered by steric shielding and length-dependent masking of reactive sites. Here, we report a facile freezing strategy that exploits ice confinement to drive highly efficient, template-free coupling of DNA oligonucleot

Для поглощения CTP хламидией трахоматисом требуется преобразование цитидина в CTP в зависимость от UCK2.

Хламидия трахоматис, обязуемая внутриклеточная бактерия, превращается в вакулярное отделение, называемое включением. бактерии импортируют нуклеосайд трифосфаты (НТФ), присутствующие в люмене для включения. Остается неясным, попадают ли нуклеозиды в люмен в их родной форме или в качестве фосфорилатированных нуклеотидов. Используя химию щелчка в сочетании с микроскопией флуоресцентной активности, мы представляем доказательства того, что цитидин требует фосфорилирования с помощью уридина-цитидиновой киназы 2 (UKK2) до его включения в бактериальные нуклеиновые кислоты. Эти выводы подтверждают гипо

Совпадение в аннотации оригинала
Chlamydia trachomatis , an obligate intracellular bacterium, develops into a vacuolar compartment called the inclusion. The bacteria import nucleoside triphosphates (NTPs) present in the inclusion lumen. It remains unclear whether nucleosides enter the inclusion lumen in their native form or as phosphorylated nucleotides. Using click chemistry coupled with f…

Synthesis of β-Cyclodextrin-Decorated Dendritic Compounds Based on EDTA Core: A New Class of PAMAM Dendrimer Analogs.

In this work, two dendritic molecules containing an ethylenediaminetetraacetic acid (EDTA) core decorated with two and four β-cyclodextrin (βCD) units were synthesized and fully characterized. Copper(I)-catalyzed alkyne-azide cycloaddition (CuAAC) click chemistry under microwave irradiation was used to obtain the target compounds with yields up to 99%. The classical ethylenediamine (EDA) core present in PAMAM dendrimers was replaced by an EDTA core, obtaining platforms that increase the water solubility at least 80 times compared with native βCD. The synthetic methodology presented here repres…

Carborane-Containing Matrix Metalloprotease (MMP) Ligands as Candidates for Boron Neutron-Capture Therapy (BNCT).

Based on the previously reported potent and selective sulfone hydroxamate inhibitors SC-76276, SC-78080 (SD-2590), and SC-77964, potent MMP inhibitors have been designed and synthesized to append a boron-rich carborane cluster by employing click chemistry to target tumor cells that are known to upregulate gelatinases. Docking against MMP-2 suggests binding involving the hydroxamate zinc-binding group, key H-bonds by the sulfone moiety with the peptide backbone residues Leu82 and Leu83, and a hydrophobic interaction with the deep P1' pocket. The more potent of the two triazole regioisomers exhi…

Double Porphyrin Cage Compounds.

The synthesis and characterization of double porphyrin cage compounds are described. They consist of two porphyrins that are each attached to a diphenylglycoluril-based clip molecule via four ethyleneoxy spacers, and are linked together by a single alkyl chain using "click"-chemistry. Following a newly developed multistep synthesis procedure we report three of these double porphyrin cages, linked by spacers of different lengths, i.e. 3, 5, and 11 carbon atoms. The structures of the double porphyrin cages were fully characterized by NMR, which revealed that they consist of mixtures of two diast

Click-to-Capture: A method for enriching viable Staphylococcus aureus using bio-orthogonal labeling of surface proteins.

Staphylococcus aureus is one of the principal causative agents of bacteremia which can progress to sepsis. Rapid diagnostic tests for identification and antibiotic resistance profiling of S. aureus would improve patient outcomes and antibiotic stewardship, but existing methods require a lengthy culture step to obtain enough material for testing. Complexity of the host matrix, where pathogenic microbes are often present, also interferes with many diagnostic methods. Here, we describe a straightforward and rapid method for enriching viable S. aureus using bio-orthogonal, or "click," chemistry me

Pathway selection between click and acyl transfer reactions driven by aminoacyl phosphates.

Covalent transformations in biology follow defined temporal sequences that regulate processes such as acylation and phosphorylation, yet achieving comparable temporal control in synthetic systems remains challenging. Here, we report an abiotic aqueous reaction network in which aminoacyl phosphate esters bearing alkyne groups undergo a programmed sequence of covalent transformations governed by peptide-based nucleophiles. Phenolic nucleophiles promote rapid copper-catalyzed azide-alkyne cycloaddition (CuAAC), whereas cysteine-containing peptides transiently coordinate copper via their thiol gro

Dynamic Self-Clickable Decellularized Matrix Hydrogels for Regulating Vascularity and Enhancing Muscle Regeneration.

Decellularized matrix (dECM) derived from small intestine submucosa (SIS) has been increasingly used in tissue engineering and regenerative medicine. While dECM provides cell-adhesive and protease-labile sequences to support cell-matrix interactions, its crosslinking into hydrogels has been largely limited to temperature-induced gelation, which offers limited tunability. To address this challenge, we previously reported the synthesis of bovine decellularized SIS-norbornene (dSIS-NB) for crosslinking into cytocompatible thiol-norbornene hydrogels with pro-angiogenic and pro-vasculogenic propert

Selective Enrichment of Newly Synthesized Proteins Using Phos-Tag Click Tip Enables Nascent Proteome Analysis in Influenza A Virus Infection.

Profiling of newly synthesized proteins (NSPs) provides access to dynamic changes in protein production that accompany acute cellular responses. Bioorthogonal noncanonical amino acid tagging (BONCAT)-based approaches enable selective labeling of NSPs; however, their broader application remains constrained by labor-intensive enrichment workflows and limited sensitivity for direct peptide-level analysis. Here, we developed a workflow termed "Phos-tag Click Tip" by integrating a phosphorylated variant of bicyclononyne (pBCN) with Phos-tag affinity purification to selectively capture azidohomoalan

Click Lipid Nanoparticles for the Delivery of mRNA to Metabolically Labeled Cancer Cells.

Lipid nanoparticle (LNP)-based mRNA delivery has a lot of potential in combating a wide range of diseases, but delivering mRNA to specific cell types continues to be challenging. Despite recent advances in organ and cell specificity, the majority of clinical LNP systems cannot fully release their payload to a targeted site. Incorporating active targeting moieties into LNPs is highly desired to expand nanomedicine applications. In this Letter, we developed LNPs that harness the power of bioorthogonal "click" azide-alkyne chemical reactions. We show that the plasma membranes of cancer cells can

Spatial Molecular Heterogeneity on Biofunctionalized Particles Quantified by Three-Dimensional Single-Molecule DNA-PAINT.

Quantifying and controlling the spatial molecular heterogeneity on biofunctionalized particles is essential for understanding and improving … molecules via two bioconjugation methods, namely, streptavidin-biotin coupling and PLL-g-PEG-based click chemistry. The data reveal interparticle and intraparticle spatial heterogeneities that are dependent on the bioconjugation methods and conditions. With the analysis framework, 3D DNA-PAINT imaging becomes a versatile characterization technique to study biofu …

EdU-Based Assay of Cell Proliferation and Stem Cell Quiescence in Skeletal Tissue Sections.

Identifying and tracking proliferating and quiescent cells in situ is an important phenotyping component of skeletal tissues in development, … more recently developed, uses 5-ethynyl-2'-deoxyuridine (EdU). This thymidine analog is detected by click chemistry, that is, covalent cross-linking of its ethynyl group with a fluorescent azide that is small enough to easily penetrate native tissues and reach DNA. In addition to being simple and quick, this EdU-based assay is compatible with other protocols, suc …

Molecular Cancer Imaging in the Second Near-Infrared Window Using a Renal-Excreted NIR-II Fluorophore-Peptide Probe.

In vivo molecular imaging of tumors targeting a specific cancer cell marker is a promising strategy for cancer diagnosis and imaging guided … cent probe is reported for molecular tumor imaging targeting a tumor stem cell biomarker CD133. The click chemistry derived peptide-dye (CP-IRT dye) probe afforded efficient in vivo tumor targeting in mice with a high tumor-to-normal tissue signal ratio (T/NT > 8). Importantly, the CP-IRT probes are rapidly renal excreted (≈87% excretion within 6 h), in stark con …

Synthesis and evaluation of disulfide bond mimetics of amylin-(1-8) as agents to treat osteoporosis.

Osteoporotic fracture is a significant public health problem, resulting in fractures in >50% of women and in almost one third of men age 65 and older. Most of the existing therapies act by slowing bone loss, through inhibiting the action of bone resorbing cells. However, more substantial reductions of fracture numbers will only result from treatments that can rebuild bone. Our own animal studies demonstrated the anabolic potential of the small but unstable octapeptide fragment of amylin-(1-37), namely amylin-(1-8) containing one disulfide bridge (Cys/2 and Cys/7) [Am. J. Physiol. Endocrinol. M

Effects of a sulfonated hydrophilic cross-linked network on the microstructure and properties of Nafion matrix.

A hydrophilic cross-linked proton exchange membrane was constructed in a Nafion matrix based on azide polysulfone containing sulfonic acid (SPSU-N3) and alkynyl substituted polyvinyl alcohol (APVA) through azide-alkyne click chemistry reaction. Arising from the increased polarity of the cross-linked network and high cross-linking density, the alcohol barrier performance of the Nafion membrane was greatly improved. The methanol permeability of the Nafion/cross-linked SPSU-N3 and APVA membrane decreases to 1.86 × 10-7 cm2 s-1, which is about 88% lower than that of the recast Nafion membrane, and…

Synthesis of an Azido-Substituted 8-Membered Ring Laddersiloxane and Its Application in Catalysis.

A first syn-type tricyclic 8-8-8 (three fused-8-membered ring) laddersiloxane functionalized with four azido groups was successfully synthesized through efficient and highly selective hydrosilylation and nucleophilic substitution, achieving an excellent overall yield. The starting material, a tetravinyl-substituted 8-8-8 laddersiloxane, was prepared via a straightforward and scalable method. The obtained azido-functionalized ladder compound, fully characterized, constitutes a versatile building block for hybrid materials. Reacting this compound with 2-ethynylpyridine via click chemistry yielde…

Construction of 1,2,3-Triazole-Embedded Polyheterocyclic Compounds via CuAAC and C-H Activation Strategies.

Over the past two decades, the copper(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition (CuAAC), commonly known as click chemistry, and C-H bond activation have gained significant attention and have emerged as key synthetic methodologies. In our efforts to synthesize fused nitrogen-containing heterocycles, we developed a palladium-catalyzed protocol for the synthesis of functionalized 7,10-dihydropyrrolo[3,2,1-ij][1,2,3]triazolo[4,5-c]quinolines and 5,8-dihydrobenzo[3,4][1,2,3]triazolo[4',5':5,6]azepino[1,2-a]indoles from suitable bromo-substituted N-propargyl-indoles. The reaction condition…

Quasi-Podands with 1,2,3-Triazole Rings from Bile Acid Derivatives: Synthesis, and Spectroscopic and Theoretical Studies.

An innovative approach to producing derivatives of bile acids has been devised, utilizing the principles of "click" chemistry. By employing intermolecular [3 + 2] cycloaddition between the newly developed acyl propiolic esters of bile acids and the azide groups of 1,3,5-tris(azidomethyl)benzene, a novel class of quasi-podands featuring 1,2,3-triazole rings has been synthesized. Identifying and characterizing these six compounds involved comprehensive analysis through spectral techniques (1H NMR, 13C NMR, and FT-IR), mass spectrometry, and the PM5 semiempirical method. The synthesized compounds

1,5-Benzodiazepines as a platform for the design of carbonic anhydrase inhibitors.

A series of novel N-triazolo-benzene sulfonamides-1,5-benzodiazepines 9a-d and 10d were designed and prepared through the copper-catalyzed azide alkyne cycloaddition click chemistry procedure, reacting the N1 -propargyl-1,5-benzodiazepine 2 and the N1 ,N5 -dipropargyl analog 6 with various benzene sulfonamide azides 8a-d. The synthesized compounds were found to show nanomolar affinity toward relevant isoforms of human carbonic anhydrase such as hCA I, II, IV, VII, IX, and XII. The divalent derivative 10d showed a particularly high inhibitory activity against all hCA isoforms when compared with…