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Usage

Uses

Used in Bioconjugation Applications:
Biotin-PEG4-N3 is used as a biotinylation reagent for labeling alkyne-containing molecules or biomolecules using either copper-catalyzed 1,3 dipolar cycloaddition click chemistry or copper-free click chemistry with cyclooctyne derivatives. The azide group reacts with alkynes to form a stable triazole linkage, facilitating the introduction of biotin into the alkyne-modified system of interest. This reaction is bioorthogonal, meaning it is compatible with biological systems as its components do not react with the biological environment.
Used in Protein Tagging:
Biotin-PEG4-N3 is used as a protein tag for non-enzymatically and covalently tagging proteins, allowing for their separation and detection using common laboratory methods such as SDS-PAGE and Western blot. It can be used in combination with other protein tags, providing flexibility in experimental design and analysis.
Used in Nanostructured Biointerfaces:
Biotin-PEG4-N3 is used in the development of nanostructured biointerfaces to study ligand and receptor spacing when different signaling molecules are present. This application aids in understanding the spatial organization and interactions of biological molecules, which is crucial for various biological processes and potential therapeutic interventions.

Upstream product

• 359860-27-8 N-(2-(2-(2-(2-amidoethoxy)ethoxy)ethoxy)ethoxy)biotinamide 
• 101187-39-7 1,11-diazido-3,6,9-trioxaundecane 
• 35013-72-0 biotin N-Hydroxysuccinimide ester 
• 134179-38-7 2-(2-(2-(2-azidoethoxy)ethoxy)ethoxy)ethylamine 
• 58-85-5 biotin 
• 112-60-7 Tetraethylene glycol 
• 33755-53-2 D-(+)-biotin 2-nitrophenyl ester 

Downstream Products

• 1246843-42-4 C₄₃H₆₁N₇O₁₁S 
• 1339202-33-3 4-((E)-(5-(2-azidoethyl)-2-hydroxyphenyl)diazenyl)-N-(13-oxo-17-((3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)-3,6,9-trioxa-12-azaheptadecyl)benzamide 
• 1428649-06-2 4-(4-{6-[(4-methoxybenzyl)imino]-2,3,4,6-tetrahydrobenzo[e]pyrimido[1,2-c][1,3]thiazin-9-yl}benzoyl)benzyl {13-oxo-17-[(3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl]-3,6,9-trioxa-12-azaheptadecyl}carbamate 
• 1428649-10-8 4-[4-(tert-butyldiphenylsilyloxymethyl)benzoyl]benzyl {13-oxo-17-[(3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl]-3,6,9-trioxa-12-azaheptadecyl}carbamate 
• 1428649-11-9 4-[4-(hydroxymethyl)benzoyl]benzyl {13-oxo-17-[(3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl]-3,6,9-trioxa-12-azaheptadecyl}carbamate 
• 1428649-12-0 4-(4-{[(4-nitrophenoxy)carbonyloxy]methyl}benzoyl)benzyl 13-oxo-17-[(3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl]-3,6,9-trioxa-12-azaheptadecylcarbamate 
• 1428649-13-1 C₅₈H₆₉BrN₈O₁₁S₂ 

Relevant academic research and scientific papers

Click chemistry-facilitated comprehensive identification of proteins adducted by antimicrobial 5-nitroimidazoles for discovery of alternative drug targets against giardiasis

Giardiasis and other protozoan infections are major worldwide causes of morbidity and mortality, yet development of new antimicrobial agents with improved efficacy and ability to override increasingly common drug resistance remains a major challenge. Antimicrobial drug development typically proceeds by broad functional screens of large chemical libraries or hypothesis-driven exploration of single microbial targets, but both strategies have challenges that have limited the introduction of new antimicrobials. Here, we describe an alternative drug development strategy that identifies a sufficient but manageable number of promising targets, while reducing the risk of pursuing targets of unproven value. The strategy is based on defining and exploiting the incompletely understood adduction targets of 5-nitroimidazoles, which are proven antimicrobials against a wide range of anaerobic protozoan and bacterial pathogens. Comprehensive adductome analysis by modified click chemistry and multidimensional proteomics were applied to the model pathogen Giardia lamblia to identify dozens of adducted protein targets common to both 5’-nitroimidazole-sensitive and-resistant cells. The list was highly enriched for known targets in G. lamblia, including arginine deiminase, α-tubulin, carbamate kinase, and heat shock protein 90, demonstrating the utility of the approach. Importantly, over twenty potential novel drug targets were identified. Inhibitors of two representative new targets, NADP-specific glutamate dehydrogenase and peroxiredoxin, were found to have significant antigiardial activity. Furthermore, all the identified targets remained available in resistant cells, since giardicidal activity of the respective inhibitors was not impacted by resistance to 5’-nitroimidazoles. These results demonstrate that the combined use of click chemistry and proteomics has the potential to reveal alternative drug targets for overcoming antimicrobial drug resistance in protozoan parasites.

The proteomic profiling of calenduloside e targets in HUVEC: Design, synthesis and application of biotinylated probe BCEA

We previously found the total saponins from the medicinal herb Aralia elata, which exhibited strong anti-oxidative and anti-apoptotic effects. calenduloside E (CE) is one of the major triterpenoid saponin compounds isolated from these total saponins. However, the endothelial protection effect and the probable protein targets of CE have not been fully characterized. In the present study, a biotin-conjugated CE analogue (BCEA) was employed as a molecular probe to research and analyse its protein targets and signaling pathways. Compared with its parental compound CE, BCEA exhibited a similar protective effect against ox-LDL induced HUVEC damage. A chemical proteomic approach identified 128 proteins that related to the cell survival signaling pathways as the targets for BCEA. Meanwhile some of these cell survival signaling pathways that showed a higher P-value in KEGG pathway analysis were associated with anti-apoptotic activity. Moreover, further evaluation with flow cytometry, JC-1 staining assays and cleaved caspase-3 activity confirmed the anti-apoptotic effect of BCEA. Taken together, these results suggested that CE can improve cell viability most likely through anti-apoptotic mechanisms, and provided the basis for the further optimization of the endothelial protection compounds.

Focusing on probe-modified peptides: A quick and effective method for target identification

A new and efficient method focusing on probe-modified peptides was developed to identify the target protein and modification site of a hit compound or a drug. This method exhibited high click conjugation efficiency and few false-positive results. The modification site further facilitated target validation, biological mechanism study and new indications exploration.

Potent Anti-SARS-CoV-2 Activity by the Natural Product Gallinamide A and Analogues via Inhibition of Cathepsin L

Cathepsin L is a key host cysteine protease utilized by coronaviruses for cell entry and is a promising drug target for novel antivirals against SARS-CoV-2. The marine natural product gallinamide A and several synthetic analogues were identified as potent inhibitors of cathepsin L with IC50 values in the picomolar range. Lead molecules possessed selectivity over other cathepsins and alternative host proteases involved in viral entry. Gallinamide A directly interacted with cathepsin L in cells and, together with two lead analogues, potently inhibited SARS-CoV-2 infection in vitro, with EC50 values in the nanomolar range. Reduced antiviral activity was observed in cells overexpressing transmembrane protease, serine 2 (TMPRSS2); however, a synergistic improvement in antiviral activity was achieved when combined with a TMPRSS2 inhibitor. These data highlight the potential of cathepsin L as a COVID-19 drug target as well as the likely need to inhibit multiple routes of viral entry to achieve efficacy.

The Synthesis and Biological Evaluation of Some C-9 and C-10 Substituted Derivatives of the RNA Polymerase i Transcription Inhibitor CX-5461

The regio-isomeric alkynyl-substituted derivatives, 2 and 3, of the RNA Polymerase I (Pol I) transcription inhibitor CX-5461 (1) were prepared and the active one (compound 3) subjected to click reactions ([3 + 2]-cycloaddition reactions) with certain alkyl azides bearing biotin or fluorescent tags. Compounds 2 and 3, as well as four [3 + 2]-cycloadducts of the latter, were subjected to biological evaluation in a human acute myeloid leukemia cell line model. Among the six compounds tested only alkyne 3 remained active but this was less potent than parent 1.

Ipomoeassin F Binds Sec61α to Inhibit Protein Translocation

Ipomoeassin F is a potent natural cytotoxin that inhibits growth of many tumor cell lines with single-digit nanomolar potency. However, its biological and pharmacological properties have remained largely unexplored. Building upon our earlier achievements

NOVEL 2,4,6-TRISUBSTITUTED S-TRIAZINE COMPOUND, PREPARATION METHOD THEREFOR, AND USE THEREOF

The present invention provides a 2,4,6-trisubstituted s-triazine compound represented by general formula (I) or pharmaceutically acceptable salts, prodrugs or solvates thereof, a preparation method therefor, and use of these compounds in preparing drugs for preventing or treating diseases associated with protein kinase and vimentin dysregulation, and cell vacuolization, and in particular, drugs for treating or preventing cancer growth and metastasis, tissue fibrosis and atherosclerosis.

Design, synthesis and biological evaluation of photoaffinity probes of antiangiogenic homoisoflavonoids

A naturally occurring homoisoflavonoid, cremastranone (1) inhibited angiogenesis in vitro and in vivo. We developed an analogue SH-11037 (2) which is more potent than cremastranone in human retinal microvascular endothelial cells (HRECs) and blocks neovascularization in animal models. Despite their efficacy, the mechanism of these compounds is not yet fully known. In the course of building on a strong foundation of SAR and creating a novel chemical tool for target identification of homoisoflavonoid-binding proteins, various types of photoaffinity probes were designed and synthesized in which benzophenone and biotin were attached to homoisoflavanonoids using PEG linkers on either the C-3′ or C-7 position. Notably, the photoaffinity probes linking on the phenol group of the C-3′ position retain excellent activity of inhibiting retinal endothelial cell proliferation with up to 72?nM of GI50.

SYNTHESIS OF NOVEL ASYMMETRIC BOW-TIE PAMAM DENDRIMER-BASED CONJUGATES FOR TUMOR-TARGETING DRUG DELIVERY

The present disclosure relates to a dendrimer-based conjugate of the formula Vm-D-C-D'-(T-F)n, which is useful for tumor targeting drug delivery. The use of asymmetric dendrimers allow for specific targeting as well as synthetic reproducibility.

Smart tools and orthogonal click-like reactions onto small unilamellar vesicles

Abstract Click-based reactions were conducted at the surface of small unilamellar vesicles (SUVs) to provide onto-vesicle chemistry with efficient innovative ready-for-use tools. For that purpose, four amphiphilic molecules were designed to insert into bi