71732-53-1

Basic information

• Product Name: Z-PHE-ALA-DIAZOMETHYLKETONE
• Synonyms: Z-PHE-ALA-DIAZOMETHYLKETONE;Z-PHE-ALA-DMK;Z-L-PHENYLALANYL-L-ALANINE-DIAZOMETHYLKETONE;carbobenzoxycarbonyl-L-phenylalanyl-L-alanine-D-diazomethane
• CAS NO: 71732-53-1
• Molecular Formula: C₂₁H₂₂N₄O₄
• Molecular Weight: 394.42
• Mol File: 71732-53-1.mol
• Article Data: 2

Chemical Properties

• Appearance: /
• Storage Temp.: -15°C
• CAS DataBase Reference: Z-PHE-ALA-DIAZOMETHYLKETONE(CAS DataBase Reference)
• NIST Chemistry Reference: Z-PHE-ALA-DIAZOMETHYLKETONE(71732-53-1)
• EPA Substance Registry System: Z-PHE-ALA-DIAZOMETHYLKETONE(71732-53-1)

Safety Data

• Hazardous Substances Data: 71732-53-1(Hazardous Substances Data)

Usage

InChI:InChI=1/C21H22N4O4/c1-15(19(26)13-23-22)24-20(27)18(12-16-8-4-2-5-9-16)25-21(28)29-14-17-10-6-3-7-11-17/h2-11,13,15,18H,12,14H2,1H3,(H2-,24,25,26,27,28)/b19-13-/t15-,18-/m0/s1

Upstream product

• 186581-53-3 diazomethane 
• 3338-39-4 N-benzyloxycarbonyl-L-phenylalanyl-L-alanine 

Downstream Products

• 150074-36-5 [(S)-1-((S)-1-Methyl-2,3-dioxo-propylcarbamoyl)-2-phenyl-ethyl]-carbamic acid benzyl ester 
• 115186-22-6 Z-L-phenylalanyl-L-alanyl bromomethyl ketone 

Relevant articles and documents

Design, synthesis and biological evaluation of potent azadipeptide nitrile inhibitors and activity-based probes as promising anti-Trypanosoma brucei agents

Trypanosoma cruzi and Trypanosoma brucei are parasites that cause Chagas disease and African sleeping sickness, respectively. There is an urgent need for the development of new drugs against both diseases due to the lack of adequate cures and emerging drug resistance. One promising strategy for the discovery of small-molecule therapeutics against parasitic diseases has been to target the major cysteine proteases such as cruzain for T. cruzi, and rhodesain/TbCatB for T. brucei. Azadipeptide nitriles belong to a novel class of extremely potent cysteine protease inhibitors against papain-like proteases. We herein report the design, synthesis, and evaluation of a series of azanitrile-containing compounds, most of which were shown to potently inhibit both recombinant cruzain and rhodesain at low nanomolar/picomolar ranges. A strong correlation between the potency of rhodesain inhibition (i.e., target-based screening) and trypanocidal activity (i.e., whole-organism-based screening) of the compounds was observed. To facilitate detailed studies of this important class of inhibitors, selected hit compounds from our screenings were chemically converted into activity-based probes (ABPs), which were subsequently used for in situ proteome profiling and cellular localization studies to further elucidate potential cellular targets (on and off) in both the disease-relevant bloodstream form (BSF) and the insect-residing procyclic form (PCF) of Trypanosoma brucei. Overall, the inhibitors presented herein show great promise as a new class of anti-trypanosome agents, which possess better activities than existing drugs. The activity-based probes generated from this study could also serve as valuable tools for parasite-based proteome profiling studies, as well as bioimaging agents for studies of cellular uptake and distribution of these drug candidates. Our studies therefore provide a good starting point for further development of these azanitrile-containing compounds as potential anti-parasitic agents. Copyright