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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
Hydrocinnamic acid is widely used as a flavoring agent and in organic synthesis. It is a volatile constituent of grapes.
Synonyms: 3-Phenylpropionic acid; 3-Phenylpropanoic acid; NSC9272
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Surveying the scope of aromatic decarboxylations catalyzed by prenylated-flavin dependent enzymes
Anushree Mondal ; Pronay Roy ; Jaclyn Carrannatto ; Prathamesh M. Datar ; Daniel J. DiRocco ; Katherine Huntera and E. Neil G. Marsh
Abstract: The prenylated-flavin mononucleotide-dependent decarboxylases (also known as UbiD-like enzymes) are the most recently discovered family of decarboxylases. The modified flavin facilitates the decarboxylation of unsaturated carboxylic acids through a novel mechanism involving 1,3-dipolar cyclo-addition chemistry. UbiD-like enzymes have attracted considerable interest for biocatalysis applications due to their ability to catalyse (de)carboxylation reactions on a broad range of aromatic substrates at otherwise unreactive carbon centres. There are now ∼35[thin space (1/6-em)]000 protein sequences annotated as hypothetical UbiD-like enzymes. Sequence similarity network analyses of the UbiD protein family suggests that there are likely dozens of distinct decarboxylase enzymes represented within this family. Furthermore, many of the enzymes so far characterized can decarboxylate a broad range of substrates. Here we describe a strategy to identify potential substrates of UbiD-like enzymes based on detecting enzyme-catalysed solvent deuterium exchange into potential substrates. Using ferulic acid decarboxylase (FDC) as a model system, we tested a diverse range of aromatic and heterocyclic molecules for their ability to undergo enzyme-catalysed H/D exchange in deuterated buffer. We found that FDC catalyses H/D exchange, albeit at generally very low levels, into a wide range of small, aromatic molecules that have little resemblance to its physiological substrate. In contrast, the sub-set of aromatic carboxylic acids that are substrates for FDC-catalysed decarboxylation is much smaller. We discuss the implications of these findings for screening uncharacterized UbiD-like enzymes for novel (de)carboxylase activity.
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Purchased from AmBeed: 27916-43-4 ; 2438-05-3 ; 501-89-3 ; 42287-94-5 ; 776-79-4 ; 53473-36-2 ; 7251-61-8 ; 42287-97-8 ; 1621-91-6 ; 37718-11-9 ; 288-13-1 ; 86-73-7 ; 104-53-0 ; 2018-90-8 ; 87-66-1 ; 135-19-3 ; 1664-57-9 ; 289-80-5 ; 693-95-8 ; 55-22-1 ; 102-93-2 ; 1477-50-5 ; 1632-76-4 ; 4780-79-4 ; 16642-79-8 ; 3581-89-3 ; 501-97-3 ; 771-50-6 ; 98-98-6 ; 619-64-7 ; 100-51-6 ; 402-45-9 ; 59-67-6 ; 93-60-7 ; 273-53-0 ; 2084-13-1 ; 51-17-2 ; 2459-09-8 ; 2459-07-6 ; 95-16-9 ; 459-31-4 ; 90-05-1 ; 150-76-5 ; 103-25-3 ; 271-44-3 ; 6293-56-7 ; 2550-26-7 ; 288-32-4 ; 501-52-0 ; 2001-32-3 ; 1592-38-7 ; 95-15-8 ; 91-19-0 ; 1122-61-8 ; 3724-19-4 ; 20173-24-4 ; 118-31-0 ; 6125-24-2 ; 60-12-8 ; 90-15-3 ; 120-72-9 ; 822-36-6 ; 288-47-1 ; 288-42-6 ; 2038-57-5 ; 38628-51-2 ; 1929-29-9 ; 15009-91-3 ; 1505-50-6 ; 581-40-8 ; 616-47-7 ; 1571-33-1
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Chen, Jing ; Ji, Peng ; Gnawali, Giri ; Chang, Mengyang ; Gao, Feng ; Xu, Hang , et al.
Abstract: The current targeting drug delivery mainly relies on cancer cell surface receptors. However, in many cases, binding affinities between protein receptors and homing ligands is relatively low and the expression level between cancer and normal cells is not significant. Distinct from conventional targeting strategies, we have developed a general cancer targeting platform by building artificial receptor on cancer cell surface via a chemical remodeling of cell surface glycans. A new tetrazine (Tz) functionalized chemical receptor has been designed and efficiently installed on cancer cell surface as "overexpressed" biomarker through a metabolic glycan engineering. Different from the reported bioconjugation for drug targeting, the tetrazine labeled cancer cells not only locally activate TCO-caged prodrugs but also release active drugs via the unique bioorthogonal Tz-TCO click-release reaction. The studies have demonstrated that the new drug targeting strategy enables local activation of prodrug, which ultimately leads to effective and safe cancer therapy.
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Keywords: Artificial receptor ; Click and release ; Local activation ; Protein degradation
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Purchased from AmBeed: 3212-75-7 ; 5505-63-5 ; 25316-40-9 ; 1345866-66-1 ; 2645443-13-4 ; 67131-33-3 ; 501-52-0 ; 1949837-12-0 ; 107-96-0 ; 78-39-7 ; 2915291-31-3
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CAS No. : | 501-52-0 |
Formula : | C9H10O2 |
M.W : | 150.17 |
SMILES Code : | O=C(O)CCC1=CC=CC=C1 |
Synonyms : |
3-Phenylpropionic acid; 3-Phenylpropanoic acid; NSC9272
|
MDL No. : | MFCD00002771 |
InChI Key : | XMIIGOLPHOKFCH-UHFFFAOYSA-N |
Pubchem ID : | 107 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
54% | N-[2-(1H-Indol-2-yl)-phenyl]-3-phenyl-propionamide Prepared from 2-(2-aminophenyl) indole and hydrocinnamic acid in 54% yield following procedure 1. The product was crystallized from methanol. 99% Purity by LC/MS (230. DAD), Mass-spec [M+H+]=341, 1H NMR (DMSO-d6): 2.65 t, 7.5 Hz (2H), 2.91 t, 7.5 Hz (2H), 6.50 s (1H), 7.00 t, 7 Hz (1H), 7.10 t, 7 Hz (1H), 7.19-7.34 m (7H), 7.39 d, 8 Hz (1H), 7.51 d, 8 Hz (1H), 7.60-7.62 m (2H), 9.39 s (1H), 11.32 s (1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In trifluoroethanol; at 20℃; for 4h; | Step A: Methyl 6-{2-[(4-chlorophenyl)amino]-1-[(2,4-dimethoxybenzyl)(3-phenylpropanoyl)-amino]-2-oxoethyl}nicotinate Dihydrocinnamic acid (46 mg, 0.30 mmol), 4-chlorophenylisocyanide (42 mg, 0.30 mmol) and 2,4-dimethoxybenzylamine (61 mg, 0.36 mmol) were added to a solution of methyl 6-formylnicotinate (see Langlois, Y. et al, Tetrahedron. 1975, 31, 419-22) (50 mg, 0.30 mmol) in 400 muL of TFE. The solution was allowed to stir for 4 h at room temperature and then purified by flash chromatography (12-100percent ethyl acetate in hexanes to give the desired product. MS cal'd 602 (MH+), exp 602 (MH+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
59% | With pyridine; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; at 50℃; for 2.0h; | A mixture of 3-phenylpropanoic acid (413 mg, 2.75 mmol), pyridine-3, 5-diamine (300 mg, 2.75 mmol) and EDCI.HC1 (580 mg, 3.03 mmol) in pyridine (5 mL) was heated at 50 C for 2 h. A black solution was formed. The mixture was concentrated and the residue was poured into water (20 mL) and stirred for 2 minutes. The aqueous layer was extracted with ethyl acetate (20 mL x3). The combined organic layer was washed with water (20 mL x2) and brine (20 mL x2), dried over anhydrous Na2S04, filtered and concentrated. The residue was purified by Combi Flash (50% to 100% EtOAc in pentane) to give N-(5-aminopyridin-3- yl)-3-phenylpropanamide (400 mg, yield: 59%) as a light yellow solid. (1398) NMR (400 MHz DMSO-rie) d 2.63 (2H, t , J= 7.7 Hz), 2.91 (2H, t , J= 7.7 Hz), 5.34 (2H, brs), 7.15-7.22 (1H, m), 7.23-7.32 (4H, m), 7.38 (1H, t, J= 2.3 Hz), 7.63 (1H, d, J= 2.5 Hz), 7.86 (1H, d, .7= 2.0 Hz), 9.83 (1H, brs). |