1137-00-4

Usage

Chemical Properties

Off-White Solid

InChI:InChI=1/C10H11N3O2/c11-8(10(14)15)4-6-5-13-9-7(6)2-1-3-12-9/h1-3,5,8H,4,11H2,(H,12,13)(H,14,15)

Upstream product

• 211179-97-4 diethyl 2-((1H-pyrrolo[2,3-b]pyridin-3-yl)methyl)-2-acetamidomalonate 
• 271-63-6 7-Azaindole 
• 4649-09-6 1H-pyrrolo[2,3-b]pyridin-3-carbaldehyde 
• 5654-92-2 7-azagramine 
• 7303-50-6 7-azatryptophan 
• 56-45-1 L-serin 
• 113975-22-7 2-fluoro-3-iodopyridine 
• 63024-18-0 N^α-Acetyl-DL-7-azatryptophan 
• 144657-73-8 tert-butyl α-amino-β-(1-tert-butyloxycarbonyl-7-azaindolyl)propionate 
• 87358-28-9 N,N,N-trimethyl-1-(1H-pyrrolo[2,3-b]pyridin-3-yl)methanaminium iodide 
• 144657-72-7 3-{(R)-2-tert-Butoxycarbonyl-2-[(1R,4R)-1,7,7-trimethyl-bicyclo[2.2.1]hept-(2E)-ylideneamino]-ethyl}-pyrrolo[2,3-b]pyridine-1-carboxylic acid tert-butyl ester 
• 144657-70-5 1-(tert-butyloxycarbonyl)-3-(iodomethyl)-7-azaindole 
• 144657-69-2 1-(tert-butyloxycarbonyl)-3-(bromomethyl)-7-azaindole 
• 144657-68-1 tert-butyl 3-(chloromethyl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate 

Downstream Products

• 1295647-38-9 (5aR,10R)-10-benzo[1,3]dioxol-5-yl-7-[(R)-1-benzylpyrrolidin-3-yl]-5,5a,7,8,10,11-hexahydro-1,7,9a,11-tetraaza-benzo[b]fluorene-6,9-dione 
• 134235-82-8 (-)-(R)-7-azatryptophan 
• 49758-35-2 (S)-2-amino-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)propanoic acid 
• 4649-12-1 2-(1H-pyrrolo[2,3-b]pyridin-3-yl)-ethylamine 
• 1200127-66-7 3-(4-(4-methylpiperazin-1-yl)phenyl)-9H-pyrrolo[2,3-b:5,4-c′]-dipyridine-6-carbonitrile 
• 1200129-93-6 C₂₂H₂₂N₆O 
• 1200129-86-7 C₂₂H₂₁N₅O₂ 
• 737007-45-3 C₂₅H₂₁N₃O₄ 

Relevant academic research and scientific papers

Chemoenzymatic synthesis of the two enantiomers of 7-azatryptophan

7-Azatryptophan is an unnatural α-amino acid with a very potent fluorescent activity. It is used as a vehicle for probing the structure and dynamics of proteins and peptides. Diastereoselective alkylation, diastereoselective protonation and enzymatic resolution have been tested for preparing enantiomerically pure 7-azatryptophan.

Biosynthesis of violacein, structure and function of L-tryptophan oxidase VioA from chromobacterium violaceum

Violacein is a natural purple pigment of Chromobacterium violaceum with potential medical applications as antimicrobial, antiviral, and anticancer drugs. The initial step of violacein biosynthesis is the oxidative conversion of L-tryptophan into the corresponding α-imine catalyzed by the flavoenzyme L-tryptophan oxidase (VioA). A substrate-related (3-(1H-indol-3-yl)-2-methylpropanoic acid) and a product-related (2-(1H-indol-3-ylmethyl)prop-2-enoic acid) competitive VioA inhibitor was synthesized for subsequent kinetic and x-ray crystallographic investigations. Structures of the binary VioA?FADH2 and of the ternary VioA?FADH2 ?2-(1H-indol-3-ylmethyl)prop-2-enoic acid complex were resolved. VioA forms a "loosely associated" homodimer as indicated by small-angle x-ray scattering experiments. VioA belongs to the glutathione reductase family 2 of FAD-dependent oxidoreductases according to the structurally conserved cofactor binding domain. The substrate-binding domain of VioA is mainly responsible for the specific recognition of L-tryptophan. Other canonical amino acids were efficiently discriminated with a minor conversion of L-phenylalanine. Furthermore, 7-aza-tryptophan, 1-methyl-tryptophan, 5-methyl-tryptophan, and 5-fluoro-tryptophan were efficient substrates of VioA. The ternary product-related VioA structure indicated involvement of protein domain movement during enzyme catalysis. Extensive structure-based mutagenesis in combination with enzyme kinetics (using L-tryptophan and substrate analogs) identified Arg64 , Lys269 , and Tyr309 as key catalytic residues of VioA. An increased enzyme activity of protein variant H163A in the presence of L-phenylalanine indicated a functional role of His163 in substrate binding. The combined structural and mutational analyses lead to the detailed understanding of VioA substrate recognition. Related strategies for the in vivo synthesis of novel violacein derivatives are discussed.

Deracemization and stereoinversion to aromatic d-amino acid derivatives with ancestral l-amino acid oxidase

Enantiomerically pure amino acid derivatives could be foundational compounds for peptide drugs. Deracemization of racemates to l-amino acid derivatives can be achieved through the reaction of evolved d-amino acid oxidase and chemical reductants, whereas deracemization to d-amino acid derivatives has not progressed due to the difficulty associated with the heterologous expression of l-amino acid oxidase (LAAO). In this study, we succeeded in developing an ancestral LAAO (AncLAAO) bearing broad substrate selectivity (13 l-amino acids) and high productivity through an Escherichia coli expression system (50.7 mg/L). AncLAAO can be applied to perform deracemization to d-amino acids in a similar way to deracemization to l-amino acids. In fact, full conversion (>99% ee, d-form) could be achieved for 16 racemates, including nine d,l-Phe derivatives, six d,l-Trp derivatives, and a d,l-phenylglycine. Taken together, we believe that AncLAAO could be a key enzyme to obtain optically pure d-amino acid derivatives in the future.

MACROCYCLIC INHIBITORS OF THE PD-1/PD-L1 AND CD80 (B7-1)/PD-LI PROTEIN/PROTEIN INTERACTIONS

The present disclosure provides novel macrocyclic peptides which inhibit the PD-1/PD-L1 and PD-L1/CD80 protein/protein interaction, and thus are useful for the amelioration of various diseases, including cancer and infectious diseases.

Directed evolution of the tryptophan synthase β-subunit for stand-alone function recapitulates allosteric activation

Enzymes in heteromeric, allosterically regulated complexes catalyze a rich array of chemical reactions. Separating the subunits of such complexes, however, often severely attenuates their catalytic activities, because they can no longer be activated by their protein partners. We used directed evolution to explore allosteric regulation as a source of latent catalytic potential using the β-subunit of tryptophan synthase from Pyrococcus furiosus (PfTrpB). As part of its native αββα complex, TrpB efficiently produces tryptophan and tryptophan analogs; activity drops considerably when it is used as a stand-alone catalyst without the α-subunit. Kinetic, spectroscopic, and X-ray crystallographic data show that this lost activity can be recovered by mutations that reproduce the effects of complexation with the α-subunit. The engineered PfTrpB is a powerful platform for production of Trp analogs and for further directed evolution to expand substrate and reaction scope.

Syntheses of a potential fluorescence probe, (-)-(R)-7-azatryptophan, via alkylation of the (1R,4R)-camphor imine of tert-butylglycinate

The synthesis of (-)-(R)-7-azatryptophan (2) from commercially available 7-azaindole (4) is described.The key step involved the diastereoselective alkylation of tert-butyl acetate (3) with 1-(tert-butyloxycarbonyl-3-(iodomethyl)-7-azaindole (14).The alkylation, conducted at -100 deg C in a THF/HMPA solvent using potassium hexamethyldisilazide as the base, afforded 7 in a greater than 98 percent diastereomeric excess.Hydrolysis and deprotecting gave (-)-(R)-7-azatryptophan.