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Sulforaphane targets Leishmania promastigotes to inhibit parasite motility and alters host autophagy to suppress parasite replication in macrophages.

UNLABELLED: Visceral leishmaniasis (VL) is a neglected tropical disease caused by the protozoan parasites Leishmania infantum (LI) and Leish … inst VL and CL parasite species at equivalent concentrations. Immunofluorescence analysis utilizing click chemistry indicated A-SFN binds to cytosolic promastigote components and colocalized only minimally with KMP-11. The binding of SFN to KMP-11 could not be confirmed in vitro. In terms of intracellular host effects, SFN treatment increased the induction of non …

Functional screening reveals Toxoplasma prenylated proteins required for endocytic trafficking and rhoptry protein sorting.

In the apicomplexans, endocytosed cargos (e.g., hemoglobin) are trafficked to a specialized organelle for digestion. This follows a unique e … d an association between protein prenylation and endocytic trafficking, and using an alkyne-labeled click chemistry approach, the prenylated proteome was characterized. Genome editing, using clustered regularly interspaced short palindromic repaet/CRISPR-associated nuclease 9 (CRISPR/Cas9), was efficiently utilized to generate genetically modified lines for the f …

[Preparation and chiral separation performance evaluation of a high performance liquid chromatography stationary phase based on a ［2+4］-type chiral porous organic cage Pim].

Porous organic cages （POCs） represent a class of emerging porous materials assembled from discrete three-dimensional cage-like molecules via … lkenyl groups using 5-bromo-1-pentene and then immobilized onto thiol-modified silica via thiol-ene click chemistry to afford a novel chiral stationary phase （CSP） for high performance liquid chromatography （HPLC）. The successful syntheses of tetraaldehyde compound， Pim， and CSP were characterized by nuclear magnetic resonance （NMR）， fourier transform infrared sp …

Bifunctional nanoparticles with magnetism and NIR fluorescence: controlled synthesis from combination of AGET ATRP and 'click' reaction.

In this work, bifunctional nanoparticles (NPs) capable of emitting near infrared (NIR) fluorescence and generating superparamagnetism under an external magnetic field were prepared by combination of 'click' reaction and surface-initiated activators generated by electron transfer for atom transfer radical polymerization (AGET ATRP) of water-soluble poly(ethylene glycol) monomethyl ether methacrylate (PEGMA) and glycidyl methacrylate (GMA) using biocompatible iron as the catalyst on the surface of silica-coated iron oxide (Fe3O4@SiO2) NPs. The nanosized Fe3O4@SiO2@PPEGMA-co-PGMA@N3 was prepared

[Injectable hydrogel microspheres experimental research for the treatment of osteoarthritis].

OBJECTIVE: To prepare a novel hyaluronic acid methacrylate (HAMA) hydrogel microspheres loaded polyhedral oligomeric silsesquioxane-diclofenac sodium (POSS-DS) patricles, then investigate its physicochemical characteristics and in vitro and in vivo biological properties. METHODS: Using sulfhydryl POSS (POSS-SH) as a nano-construction platform, polyethylene glycol and DS were chemically linked through the "click chemistry" method to construct functional nanoparticle POSS-DS. The composition was analyzed by nuclear magnetic resonance spectroscopy and the morphology was characterized by transmis…

[Role of protein palmitoylation modification in the proliferation and gametogenesis of Plasmodium falciparum].

OBJECTIVE: To investigate the palmitoyltransferase (PATs) activity during different developmental stages of Plasmodium falciparum and to explore the impact of PATs activity on intra-erythrocytic replication and gametocytogenesis, so as to provide insights into development of novel antimalarial targets. METHODS: The PATs activity was measured using the click chemistry method during different developmental stages of P. falciparum, including rings, trophozoites, schizonts, and gametocytes. P. falciparum-infected erythrocytes were divided into three groups, including a control group, a dimethyl s…

[Using activity-based protein profiling method to explore the antitumor targets of spiramycin derivatives].

Carrimycin is a macrolide antibiotic widely used in the pharmaceutical and clinical fields， with its primary composition consisting of three … affinity-based enrichment techniques-specifically via copper-catalyzed azide-alkyne cycloaddition （click chemistry） to immobilize them onto a solid support. The enriched protein pool was then subjected to in-depth analysis using liquid chromatography-mass spectrometry （LC-MS）. This analytical phase yielded detailed， proteome-wide information on the identities of …

Analysis of microRNA expression profiles in exosomes derived from acute myeloid leukemia by p62 knockdown and effect on angiogenesis.

ObjectivesIn this study, we aimed to investigate the effect of p62 on angiogenesis and microRNA (miRNA) expression profiles in acute myeloid leukemia (AML) exosomes.MethodsAn Exiqon v19.0 microRNA MicroArray was used to profile miRNAs in exosomes derived from parental and p62-knockdown U937 cells. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases were used to predict the biological functions and potential mechanisms of differentially expressed miRNAs in AML exosomes. Endothelial cell tube formation assays using human umbilical vein endothelial cells (HUVECs) w

Advances in Peptidomimetics for Next-Generation Therapeutics: Strategies, Modifications, and Applications.

Over the past two decades, peptide drug discovery has experienced a remarkable renaissance, with organic chemistry and biotechnology emerging as pivotal tools for developing peptidomimetics that exhibit improved stability, specificity, and bioavailability compared to conventional peptides. This review systematically examines methodologies for modifying peptide backbones to achieve targeted properties, highlighting recent advances facilitated by modern biotechnological innovations for novel molecular transformations. Additionally, the review emphasizes the practical applications of peptides and

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… Similarly, click chemistry stapling techniques can confer stability to β-turns and β-hairpins. Macrocyclic peptides have demonstrated suitability as pharmaceuticals and recent advances have moved beyond mimicking natural cyclic peptides. … In general, stapling methods involving natural amino acids, Grubbs catalysts, or click chemistry constitute one-component stapling techniques, allowing the direct coupling of complementary side-chain groups. …

Clinicopathological findings of FeLV- positive cats at a secondary referral center in Florida, USA (2008-2019).

OBJECTIVES: The aim of this study was to describe the seroprevalence, presenting complaint, clinicopathological changes, co-morbidities and outcomes of feline leukemia virus positive cats presented to a specialty referral center in Florida, USA. METHODS: In this retrospective study, medical records of 8050 cats presented to a private referral center from August 2008 to September 2019 were reviewed. Inclusion criteria required was a positive result for feline leukemia virus by point-of-care antigen testing or immunofluorescence assay. RESULTS: Forty-one cases met the inclusion criteria. Of 20

Applications of synthetic biology in medical and pharmaceutical fields.

Synthetic biology aims to design or assemble existing bioparts or bio-components for useful bioproperties. During the past decades, progresses have been made to build delicate biocircuits, standardized biological building blocks and to develop various genomic/metabolic engineering tools and approaches. Medical and pharmaceutical demands have also pushed the development of synthetic biology, including integration of heterologous pathways into designer cells to efficiently produce medical agents, enhanced yields of natural products in cell growth media to equal or higher than that of the extract

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… Genetically encoded click chemistry in medical applications Inspired by click chemistry, isopeptide bond was engineered for the establishment of protein-protein linkages. 251 The genetic-encoded click chemistry is more applicable in living organisms compared with traditional click chemistry. … The proteins were turned into a high-mechanical strength hydrogel, allowing mouse embryonic stem cells to maintain pluri-potentials without adding other cytokines in the gel. 260 Genetically encoded click chemistry has also used in the vaccine development. …

The KISS1 Receptor as an In Vivo Microenvironment Imaging Biomarker of Multiple Myeloma Bone Disease.

Multiple myeloma is one of the most common hematological diseases and is characterized by an aberrant proliferation of plasma cells within the bone marrow. As a result of crosstalk between cancer cells and the bone microenvironment, bone homeostasis is disrupted leading to osteolytic lesions and poor prognosis. Current diagnostic strategies for myeloma typically rely on detection of excess monoclonal immunoglobulins or light chains in the urine or serum. However, these strategies fail to localize the sites of malignancies. In this study we sought to identify novel biomarkers of myeloma bone di

Biosynthesis of anticancer phytochemical compounds and their chemistry.

Cancer is a severe health issue, and cancer cases are rising yearly. New anticancer drugs have been developed as our understanding of the molecular mechanisms behind diverse solid tumors, and metastatic malignancies have increased. Plant-derived phytochemical compounds target different oncogenes, tumor suppressor genes, protein channels, immune cells, protein channels, and pumps, which have attracted much attention for treating cancer in preclinical studies. Despite the anticancer capabilities of these phytochemical compounds, systemic toxicity, medication resistance, and limited absorption re

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… Tasumatrol B showed significant cytotoxicity compared to other compounds | Qayum et al. (2019) Binding energy range: 6.9 kcal/mol to -7.1 kcal/mol 2 | Chemical Synthesis by click chemistry | Topoisomerase | Podophyllotoxin-glycerol triazoles | MTT assay was performed using Du145, A-549, MCF-7 and HeLa …

Natural extract-derived compounds for the treatment of hematological diseases through modulation of the bone marrow microenvironment.

The bone marrow microenvironment comprises a complex network of hematopoietic stem cells, immune cells, stromal cells, and non-cellular components such as the extracellular matrix and soluble factors, collectively maintaining the homeostasis of hematopoietic stem and progenitor cells. It is highly vulnerable to pathological perturbations induced by hematologic malignancies, solid tumors, inflammatory stress, and therapeutic exposure, which collectively destabilize microenvironmental homeostasis and promote hematopoietic failure, malignant progression, and immune dysregulation. Natural products

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… The application of click chemistry reactions (CuAAC/SPAAC) enables site-specific modification of exosomal membrane proteins, facilitating the construction of chimeric antigen receptor-modified sEVs (CAR-sEVs) ( Lu et al., 2025 ). … Click chemistry facilitates precise modifications to functional groups. This technique enables specific conjugation while preserving the integrity of the natural product backbone, ensuring that exosome activity is maintained ( Lu et al., 2025 ). …

Биологическая роль мономеров традиционной китайской медицины в нейронных расстройствах.

Традиционная китайская медицина (TCM) является биоактивным соединением, извлекаемым из китайских травяных лекарственных препаратов, обладающих определенной биологической активностью и фармакологическими последствиями, и привлекла большое внимание к лечению нейронных заболеваний. Однако применение мономеров ТХМ ограничено их низкой растворимостью и низкой способностью пересекать барьер кровеносного мозга (ББД). Экзосомы представляют собой небольшие внеклеточные везикли (ЭМ) диаметром от 30 до 150 нм и могут использоваться в качестве носителей наркотиков, которые непосредственно предназначены дл

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… Genetic engineering and click chemistry are widely used approaches to produce surface-modified exosomes. … Zheng et al. [ 22 ] first designed and synthesized five N -acyl side chain sialic acid analogs of different lengths and then screened the best metabolic precursors for exosome labeling through biorthogonal click chemistry. …

Targeted Protein Degradation in Cancer: PROTACs, New Targets, and Clinical Mechanisms.

The onset of proteolysis targeting chimeras (PROTACs) has reshaped the entire context of targeted cancer therapy by offering a novel approach for the selective degradation of disease-causing proteins, overcoming the limitations of traditional occupancy-driven inhibition. This heterobifunctional technology recruits endogenous E3 ubiquitin ligases to mark proteins of interest (POI) for proteosomal degradation via the ubiquitin-proteasome system (UPS). Unlike conventional inhibitors, PROTACs function catalytically and can target previously "undruggable proteins", such as transcription factors, sc

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… Additionally, in-cell click chemistry approaches now enable the intracellular assembly of PROTACs to enhance bioavailability and minimize off-target effects through localization. Their activity is directed at specific cellular compartments. … Click Chemistry in the Development of PROTACs RSC Chem. Biol. 2023 5 189 10.1039/D3CB00199G 38456041 PMC10915971 42. Imaide S. Riching K.M. Makukhin N. Vetma V. Whitworth C. Hughes S.J. Trainor N. Mahan S.D. Murphy N. Cowan A.D. …

Dendrimer-doxorubicin conjugates exhibit improved anticancer activity and reduce doxorubicin-induced cardiotoxicity in a murine hepatocellular carcinoma model.

Hepatocellular carcinoma (HCC) is the 2nd leading cause of cancer-related deaths every year globally. The most common form of treatment, hepatic arterial infusion (HAI), involves the direct injection of doxorubicin (DOX) into the hepatic artery. It is plagued with limited therapeutic efficacy and the occurrence of severe toxicities (e.g. cardiotoxicity). We aim to improve the therapeutic index of DOX delivered via HAI by loading the drug onto generation 5 (G5) poly(amidoamine) (PAMAM) dendrimers targeted to hepatic cancer cells via N-acetylgalactosamine (NAcGal) ligands. DOX is attached to the

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… PEG in the brush conformation completely covers the G5 surface, preventing protein adsorption that would lead to clearance of the particles by the reticuloendothelial system (RES).[ 27 , 34 , 35 ] Next, we conjugated L3-DOX or L4-DOX linkages onto PEGylated G5 using click chemistry[ 26 , 27 ] to achieve …

Effect of combining glucocorticoids with Compound A on glucocorticoid receptor responsiveness in lymphoid malignancies.

Glucocorticoids (GCs) are a cornerstone in the treatment of lymphoid malignancies such as multiple myeloma (MM) and acute lymphoblastic leukemia (ALL). Yet, prolonged GC use is hampered by deleterious GC-related side effects and the emergence of GC resistance. To tackle and overcome these GC-related problems, the applicability of selective glucocorticoid receptor agonists and modulators was studied, in search of fewer side-effects and at least equal therapeutic efficacy as classic GCs. Compound A (CpdA) is a prototypical example of such a selective glucocorticoid receptor modulator and does no

A review on gold nanoparticles as an innovative therapeutic cue in bone tissue engineering: Prospects and future clinical applications.

Bone damage is a complex orthopedic problem primarily caused by trauma, cancer, or bacterial infection of bone tissue. Clinical care management for bone damage remains a significant clinical challenge and there is a growing need for more advanced bone therapy options. Nanotechnology has been widely explored in the field of orthopedic therapy for the treatment of a severe bone disease. Among nanomaterials, gold nanoparticles (GNPs) along with other biomaterials are emerging as a new paradigm for treatment with excellent potential for bone tissue engineering and regenerative medicine application

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… chemistry GNPs can be functionalized using click chemistry, a versatile and highly efficient method for attaching specific functional groups to the nanoparticle surface, enabling a wide range of applications in diagnostics, sensing, and drug delivery. [ 200 ] Electrostatic adsorption GNPs can undergo … chemistry | GNPs can be functionalized using click chemistry, a versatile and highly efficient method for attaching specific functional groups to the nanoparticle surface, enabling a wide range of applications in diagnostics, sensing, and drug delivery. | [ 200 ] Electrostatic adsorption | GNPs can …

Covalent targeting of PSMD14 by Eupalinolide B induces oncoprotein degradation and apoptosis in acute promyelocytic leukemia cells.

Treatment of acute promyelocytic leukemia (APL) remains challenged by toxicities associated with current regimens, highlighting the need for novel and safer therapeutic agents. Here, we identify Eupalinolide B (EB), a natural sesquiterpene lactone isolated from Eupatorium lindleyanum DC., as a potent anti-leukemic compound targeting the human APL-derived HL-60 cell line. Through integrated chemoproteomic profiling and functional validation, we demonstrate that EB covalently binds and inhibits 26S proteasome non-ATPase regulatory subunit 14 (PSMD14), a deubiquitinase enzyme (DUB) within the 19S

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… Cells were permeabilized with 0.2% Triton X-100 for 15 min, followed by the addition of the click chemistry reaction mixture as described above. Subsequently, cells were stained with Hoechst nuclear dye for 20 min at room temperature and washed twice with PBS. … For fluorescence colocalization assays, after the click chemistry reaction and PBS washes, cells were incubated with primary antibody against PSMD14 (1 : 200) at 4 °C for 12 h, followed by two PBS washes. …