908007-17-0

Usage

Uses

Used in Biochemistry and Molecular Biology:
N-(3-Azidopropyl)biotinamide is used as a reactant in the synthesis of clickable coumarins, which serve as fluorescent labels for amino acids. This application is particularly useful for researchers who need to track and visualize specific amino acids within complex biological systems, aiding in the study of protein interactions and functions.

Upstream product

• 88192-19-2 3-azidopropylamine 
• 58-85-5 biotin 
• 72320-38-8 3-azidopropan-1-ol 
• 35013-72-0 biotin N-Hydroxysuccinimide ester 

Relevant academic research and scientific papers

Site-specific protein modification through CuI-catalyzed 1,2,3-triazole formation and its implementation in protein microarray fabrication

(Figure Presented) Out of site: A protein expression system was combined with CuI-catalyzed 1,2,3-triazole formation to modify a target protein at its C terminus. The immobilized core protein can be modified by diverse small molecules in a site

Construction of polymer-protein bioconjugates with varying chain topologies: Polymer molecular weight and steric hindrance effects

We report on the fabrication of well-defined polymer-protein bioconjugates with varying chain architectures, including star polymers, star block copolymers, and heteroarm star copolymers through the specific noncovalent interaction between avidin and biotinylated synthetic polymer precursors. Homopolymer and diblock precursors site-specifically labeled with a single biotin moiety at the chain terminal, chain middle, or diblock junction point were synthesized by a combination of atom-transfer radical polymerization (ATRP) and click reactions. By taking advantage of molecular recognition between avidin and biotin moieties, supramolecular star polymers, star block copolymers, and heteroarm star copolymers were successfully fabricated. This specific binding process was also assessed by using the diffraction optic technology (DOT) technique. We further investigated the effects of polymer molecular weights, location of biotin functionality within the polymer chain, and polymer chain conformations, that is, steric hindrance effects, on the binding numbers of biotinylated polymer chains per avidin within the polymer-protein bioconjugates, which were determined by the standard avidin/2-(4- hydroxyazobenzene)benzoic acid (HABA) assay. The binding numbers vary in the range of 1.9-3.3, depending on the molecular weights, locations of biotin functionality within synthetic polymer precursors, and polymer chain conformations.

Photoaffinity Probe Reveals the Potential Target of Harringtonolide for Cancer Cell Migration Inhibition

Harringtonolide (HO, 1) is a bioactive diterpenoid tropone isolated from Cephalotaxus harringtonia with antiproliferation activity. Until now there have been no reports to elucidate its anticancer mechanism. Herein we report the synthesis of HO-derived probes (10, 11, and 12) to identify the possible target of HO. As a result, the application of a novel photoaffinity alkyne-tagged probe from HO (compound 12) showed direct engagement between HO and receptor for activated C kinase 1 (RACK1). Furthermore, HO could suppress the epithelial-mesenchymal transition (EMT) process and inhibit activation of the FAK/Src/STAT3 signaling pathway in A375 cells. This study provides a groundwork for HO as an effective antitumor agent that targets RACK1 to suppress cancer cell migration.

Chemical Probes Reveal Sirt2's New Function as a Robust "eraser" of Lysine Lipoylation

Lysine lipoylation, a highly conserved lysine post-translational modification, plays a critical role in regulating cell metabolism. The catalytic activity of a number of vital metabolic proteins, such as pyruvate dehydrogenase (PDH), depends on lysine lipoylation. Despite its important roles, the detailed biological regulatory mechanism of lysine lipoylation remains largely unexplored. Herein we designed a powerful affinity-based probe, KPlip, to interrogate the interactions of lipoylated peptide/proteins under native cellular environment. Large-scale chemical proteomics analysis revealed a number of binding proteins of KPlip, including sirtuin 2 (Sirt2), an NAD+-dependent protein deacylase. To explore the potential activity of Sirt2 toward lysine lipoylation, we designed a single-step fluorogenic probe, KTlip, which reports delipoylation activity in a continuous manner. The results showed that Sirt2 led to significant delipoylation of KTlip, displaying up to a 60-fold fluorescence increase in the assay. Further kinetic experiments with different peptide substrates revealed that Sirt2 can catalyze the delipoylation of peptide (DLAT-PDH, K259) with a remarkable catalytic efficiency (kcat/Km) of 3.26 × 103 s-1 M-1. The activity is about 400-fold higher than that of Sirt4, the only mammalian enzyme with known delipoylation activity. Furthermore, overexpression and silencing experiments demonstrated that Sirt2 regulates the lipoylation level and the activity of endogenous PDH, thus unequivocally confirming that PDH is a genuine physiological substrate of Sirt2. Using our chemical probes, we have successfully established the relationship between Sirt2 and lysine lipoylation in living cells for the first time. We envision that such chemical probes will serve as useful tools for delineating the roles of lysine lipoylation in biology and diseases.

A biotin-conjugated photo-Activated CO-releasing molecule (biotinCORM): Efficient CO-release from an avidin-biotinCORM protein adduct

Biotinylated pharmaceuticals are of great interest due to the strong interactions between biotinyl-functionality and streptavidin/avidin, which opens up avenues for efficient targeting and localisation. Three new carbon monoxide-releasing molecules (CO-RMs) have been synthesised and characterised using chemical and biological analysis. An alkyne-containing CO-RM 2 was found to be toxic to RAW 264.7 murine macrophages; and thus therapeutically viable CO-RM 1 was employed as the alkyne precursor for [3 + 2] cycloaddition chemistry enabling a new acid-containing CO-RM 4 and biotin-bioconugate-CO-RM (BiotinCORM 5) to be prepared. CO-RM 4 showed significantly improved solubility and BiotinCORM 5 acts as a photo-CO-RM. We have found that an avidin-CORM adduct of 5 is a CO-releasing protein, releasing CO on irradiation with light (400 nm). The avidin-biotinCORM adduct of 5 was found to have a binding energy of 10 kcal mol-1.

NOVEL COMPOUNDS AND USES

The present invention relates to compounds of formula (I): wherein Q is O or S; R1 is a cyclic group substituted with at least one group X, wherein R1 may optionally be further substituted; X is any group comprising a carbonyl group; and R2 is a cyclic group substituted at the α-position, wherein R2 may optionally be further substituted. The present invention further relates to salts, solvates and prodrugs of such compounds, to pharmaceutical compositions comprising such compounds, and to the use of such compounds in the treatment and prevention of medical disorders and diseases, most especially by the dual action of NLRP3 inhibition and the stimulation of insulin secretion.

Alkynyl sugar analogs for labeling and visualization of glycoconjugates in cells

Methods for metabolic oligosaccharide engineering that incorporates derivatized alkyne-bearing sugar analogs as “tags” into cellular glycoconjugates are disclosed. Alkynyl derivatized Fuc and alkynyl derivatized ManNAc sugars are incorporated into cellular glycoconjugates. Chemical probes comprising an azide group and a visual or fluorogenic probe and used to label alkyne-derivatized sugar-tagged glycoconjugates are disclosed. Chemical probes bind covalently to the alkynyl group by Cu(I)-catalyzed [3+2] azide-alkyne cycloaddition and are visualized at the cell surface, intracellularly, or in a cellular extract. The labeled glycoconjugate is capable of detection by flow cytometry, SDS-PAGE, Western blot, ELISA, confocal microscopy, and mass spectrometry.

SULFONYLUREAS AND RELATED COMPOUNDS AND USE OF SAME

ABSTRACT The present invention provides for certain sulfonyl ureas and related compounds which have advantageous properties and show useful activity in the inhibition of activation of the NLRP3 inflammasome. Such compounds are useful in the treatment of a wide range of disorders in which the inflammation process, or more specifically the NLRP3 inflammasome, have been implicated as being a key factor.

Fluorescent Probes for Single-Step Detection and Proteomic Profiling of Histone Deacetylases

Histone deacetylases (HDACs) play important roles in regulating various physiological and pathological processes. Developing fluorescent probes capable of detecting HDAC activity can help further elucidate the roles of HDACs in biology. In this study, we first developed a set of activity-based fluorescent probes by incorporating the Kac residue and the O-NBD group. Upon enzymatic removal of the acetyl group in the Kac residue, the released free amine reacted intramolecularly with the O-NBD moiety, resulting in turn-on fluorescence. These designed probes are capable of detecting HDAC activity in a continuous fashion, thereby eliminating the extra step of fluorescence development. Remarkably, the amount of turn-on fluorescence can be as high as 50-fold, which is superior to the existing one-step HDAC fluorescent probes. Inhibition experiments further proved that the probes can serve as useful tools for screening HDAC inhibitors. Building on these results, we moved on and designed a dual-purpose fluorescent probe by introducing a diazirine photo-cross-linker into the probe. The resulting probe was not only capable of reporting enzymatic activity but also able to directly identify and capture the protein targets from the complex cellular environment. By combining a fluorometric method and in-gel fluorescence scanning technique, we found that epigenetic readers and erasers can be readily identified and differentiated using a single probe. This is not achievable with traditional photoaffinity probes. In light of the prominent properties and the diverse functions of this newly developed probe, we envision that it can provide a robust tool for functional analysis of HDACs and facilitate future drug discovery in epigenetics.

Synthesis and properties of a biotin-tagged NHC-gold complex

The first synthesis of a biotin-tagged NHC-gold complex is described. The key step is the coupling of alkyne-substituted biotin derivative 4b with azido-imidazolium salt 8a by copper-catalyzed azide alkyne cycloaddition (CuAAC). Gold complex 2 catalyzes the cycloisomerization of α-hydroxyallenes to 2,5-dihydrofurans.