25055-84-9

Upstream product

• 98-59-9 p-toluenesulfonyl chloride 
• 25055-82-7 3-(2-hydroxyethyl)-3-methyl-3H-diazirine 

Downstream Products

• 136353-73-6 S-(3-azibutyl) thiobenzoate 
• 1620483-24-0 N-[2-(3-methyl-3H-diaziren-3-yl)ethyl]-2-nitro-N-(2-propyn-1-yl)benzenesulfonamide 
• 1620483-11-5 {4-[2-(3-methyl-3H-diaziren-3-yl)ethoxy]phenyl}methanol 

Relevant academic research and scientific papers

Non-natural amino acid and application thereof in protein site-specific modification and protein interaction

The invention relates to a non-natural amino acid compound represented by a general formula (I) and a preparation method thereof, and applications of the non-natural amino acid compound in fixed-pointmodification of bio-macro-molecular proteins, protein i

BIS(DIAZIRINE) DERIVATIVES AS PHOTO-CROSSSLINKER FOR TREATING CORNEAL ECTATIC DISORDERS

This disclosure features bis(diazirine) derivatives of the formulae (I) (l-a) or (l-b) that generate cross-linking in the cornea in response to exposure to an electromagnetic irradiation (e.g. UV-light). The compounds are useful, e.g. for treating a subje

Photoaffinity palladium reagents for capture of protein-protein interactions

Protein-protein interactions (PPIs) are indispensable in almost all cellular processes. Probing of complex PPIs provides new insights into the biological system of interest and paves the way for the development of therapeutics. Herein, we report a strategy for the capture of protein-protein interactions using photoaffinity palladium reagents. First, the palladium-mediated reagent site specifically transferred a photoaffinity modified aryl group to the designated cysteine residue. Next, the photoaffinity group was activated by UV radiation to trap the proximal protein residue for the formation of a crosslink. This strategy was used to capture the PYL-ABA-PP2C interaction, which is at the core of the abscisic acid (ABA) signalling pathway. Our results indicated that this palladium-mediated strategy can serve as an alternative for incorporating an increasing number of diverse substrates for protein crosslinking through cysteine modifications and can be explored for use in mapping protein-peptide or protein-protein interaction surfaces and in trapping potential interacting partners.

Chemical Synthesis of Diubiquitin-Based Photoaffinity Probes for Selectively Profiling Ubiquitin-Binding Proteins

Biochemical studies of cellular processes involving polyubiquitin have gained increasing attention. More tools are needed to identify ubiquitin (Ub)-binding proteins. We report diazirine-based photoaffinity probes that can capture Ub-binding proteins in c

Mapping the protein interaction landscape for fully functionalized small-molecule probes in human cells

Phenotypic screening provides a means to discover small molecules that perturb cell biological processes. Discerning the proteins and biochemical pathways targeted by screening hits, however, remains technically challenging. We recently described the use of small molecules bearing photoreactive groups and latent affinity handles as fully functionalized probes for integrated phenotypic screening and target identification. The general utility of such probes, or, for that matter, any small-molecule screening library, depends on the scope of their protein interactions in cells, a parameter that remains largely unexplored. Here, we describe the synthesis of an ～60-member fully functionalized probe library, prepared from Ugi-azide condensation reactions to impart structural diversity and introduce diazirine and alkyne functionalities for target capture and enrichment, respectively. In-depth mass spectrometry-based analysis revealed a diverse array of probe targets in human cells, including enzymes, channels, adaptor and scaffolding proteins, and proteins of uncharacterized function. For many of these proteins, ligands have not yet been described. Most of the probe-protein interactions showed well-defined structure-activity relationships across the probe library and were blocked by small-molecule competitors in cells. These findings indicate that fully functionalized small molecules canvas diverse segments of the human proteome and hold promise as pharmacological probes of cell biology.

Development of tag-free photoprobes for studies aimed at identifying the target of novel Group A Streptococcus antivirulence agents

We previously reported the identification and development of novel inhibitors of streptokinase (SK) expression by Group A Streptococcus (GAS), originating from a high throughput cell-based phenotypic screen. Although phenotypic screening is well-suited to

ITRACONAZOLE ANALOGS AND USE THEREOF

Provided herein are Itraconazole analogs. Also provided herein are methods of inhibition of Hedgehog pathway, vascular endothelial growth factor receptor 2 (VEGFR2) glycosylation, angiogenesis and treatment of disease with Itraconazole analogs.

Itraconazole Side Chain Analogues: Structure-Activity Relationship Studies for Inhibition of Endothelial Cell Proliferation, Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) Glycosylation, and Hedgehog Signaling

Itraconazole is an antifungal drug that was recently found to possess potent antiangiogenic activity and anti-hedgehog (Hh) pathway activity. To search for analogues of itraconazole with greater potency and to understand the structure-activity relationship in both antiangiogenic and Hh targeting activity, 25 itraconazole side chain analogues were synthesized and assayed for inhibition of endothelial cell proliferation and Gli1 transcription in a medulloblastoma (MB) culture. Through this analysis, we have identified analogues with increased potency for inhibiting endothelial cell proliferation and the Hh pathway, as well as VEGFR2 glycosylation that was recently found to be inhibited by itraconazole. An SAR analysis of these activities revealed that potent activity of the analogues against VEGFR2 glycosylation was generally driven by side chains of at least four carbons in composition with branching at the α or β position. SAR trends for targeting the Hh pathway were divergent from those related to HUVEC proliferation or VEGFR2 glycosylation. These results also suggest that modification of the sec-butyl side chain can lead to enhancement of the biological activity of itraconazole.

Photoaffinity-labeled peptoids and depsipeptides by multicomponent reactions

Photoaffinity tags can be incorporated easily into peptoids and congeners by the Ugi and Passerini multicomponent reactions. Products related to photo-methionine and photo-leucine can be accomplished by diazirine-containing building blocks. The same proto