2566-22-5Relevant articles and documents
An expedient synthesis of N-(1-(5-mercapto-4-((substituted benzylidene)amino)-4H-1,2,4-triazol-3-yl)-2-phenylethyl)benzamides as jack bean urease inhibitors and free radical scavengers: Kinetic mechanism and molecular docking studies
Saeed, Aamer,Larik, Fayaz Ali,Channar, Pervaiz Ali,Mehfooz, Haroon,Ashraf, Mohammad Haseeb,Abbas, Qamar,Hassan, Mubashir,Seo, Sung-Yum
, p. 764 - 777 (2017)
In this study, some new azomethine-triazole hybrids 5a–5l derived from N-benzoyl-L-phenylalanine were synthesized and characterized. The synthesized compounds showed first-rate, urease inhibition, and compounds 5c and 5e were found to be most effective inhibitors with 0.0137?±?0.00082?μm and 0.0183?±?0.00068?μm, respectively (thiourea 15.151?±?1.27?μm). The kinetic mechanism of urease inhibition revealed the compounds 5c and 5e to be non-competitive inhibitors, whereas compounds 5d and 5j were found to be of mixed-type inhibitors. Docking studies also indicated better interaction patterns with urease enzyme. The results of enzyme inhibition, kinetic mechanism and molecular docking suggest that these compounds can serve as lead compounds in the design of more effective urease inhibitors.
N-BENZOYLPHENYLALANINE AND N-BENZOYLPHENYLALANINOL, AND THEIR BIOSYNTHESIS IN PENICILLIUM BREVICOMPACTUM
Doerfler, Dennis L.,Bird, Bruce A.,Campbell, Iain M.
, p. 2303 - 2304 (1981)
N-Benzoylphenylalanine and N-benzoylphenylalaninol have been detected in cultures of Penicillium brevicompactum.Isotope from phenylalanine was incorporated effectively into the benzoyl group of both compounds.Key Word Index- Penicillium brevicompactum; fungus; biosynthesis; N-benzoylphenylalanine; N-benzoylphenylalninol.
Inhibition effects in the hydrolysis reactions of esters and peptides catalyzed by carboxypeptidase A: An example of cooperative binding effects with a monomeric enzyme
Rahmo, Abdulkader,Fife, Thomas H.
, p. 226 - 241 (2000)
N-benzoyl-L-phenylalanyl-L-phenylalanine is an excellent peptide substrate for carboxypeptidase A; at 30°C and pH 7.5, Km is 2.6 × 10-5 M while κcat is 177 s-1 κcat/Km = 6.8 × 106 M-1 s-1). Indole-3-acetic acid is a noncompetitive or mixed inhibitor towards the peptide and toward hippuryl-L-phenylalanine; plots of E/V vs [Inhibitor] are linear. N-Benzoyl-L-phenylalanine is a competitive inhibitor of peptide hydrolysis, and plots of E/V vs [Inhibitor] are again linear. One molecule of inhibitor binds per active site, and these inhibitors bind in different sites. At constant peptide substrate concentration and a series of constant concentrations of indole-3-acetic acid, plots of E/V vs the concentration of N-benzoyl-L-phenylalanine are linear and intersect behind the E/V axis and above the [Inhibitor] axis. This shows that both inhibitors can bind simultaneously and that binding of one facilitates the binding of the other (β = 0.18). Employing the ester substrate hippuryl-DL,βphenyllactate, the same type of behavior is observed in the reverse sense; N-benzoyl-L-phenylalanine is a linear noncompetitive inhibitor and indole-3-acetic acid is a linear competitive inhibitor. Again the two inhibitor plot is linear and intersects above the [Inhibitor] axis (β = 0.12). Previous X-ray crystallographic studies have indicated that indole-3-acetic acid binds in the hydrophobic pocket of the S1 site, while N-benzoyl-L-phenylalanine binds in the S1-S2 site. The product complex for hydrolysis of N-benzoyl-L-phenylalanyl-L-Phenylalanine (phenylalanine + N-benzoyl-L-phenylalanine) occupies both of these sites. However, the present work shows that the peptide substrate does not bind to the enzyme at pH 7.5 so as to be competitive with indole-3-acetic acid. The binding sites may be formed via conformational changes induced or stabilized by substrate and product binding.
OCCURRENCE AND BIOSYNTHESIS OF ASPERPHENAMATE IN SOLID CULTURES OF PENICILLIUM BREVICOMPACTUM
Bird, Bruce A.,Campbell, Iain M.
, p. 2405 - 2406 (1982)
The ester of N-benzoylphenylalanine and N-benzoylphenylalaninol, asperphenamate, was isolated from solid cultures of Penicillium brevicompactum.Isotope from L-phenylalanine was well incorporated into both benzoyl groups and into the phenylalanine and phenylalaninol moieties.Isotope from benzoic acid was also well incorporated into asperphenamate.Key Word Index-Penicillium brevicompactum; Hyphomycetes; fungus; biosynthesis; asperphenamate; phenylalanine derivatives.
Tuning lipase enantioselectivity in organic media using solid-state buffers
Quiros,Parker,Turner
, p. 5074 - 5079 (2001)
The enantioselectivity exhibited by Candida antarctica lipase B (CALB) in predominantly organic media has been studied for different enzyme protonation states. Alcoholysis of (±)-2-phenyl-4-benzyloxazol-5(4H)-one (1) using butan-1-ol as the nucleophile in low-water organic solvents was used as a model reaction. Using either organo-soluble bases or the newly introduced solid-state buffers of known pKa, the protonation state of the lipase was altered. By choice of the appropriate solid-state buffer or organic base, the enantioselectivity could be selectively tuned. Both Et3N and the solid-state buffer pair CAPSO/CAPSO.Na were found to increase the enantioselectivity of the reaction catalyzed by CALB and that of another lipase (Mucor miehei). Significant differences to both the enantioselectivity and catalytic rate were observed, especially under hydrated conditions where byproduct acid was formed.
Electrophilic Sulfonium-Promoted Peptide and Protein Amidation in Aqueous Media
Wan, Chuan,Feng, Yuan,Hou, Zhanfeng,Lian, Chenshan,Zhang, Liang,An, Yuhao,Sun, Jinming,Yang, Dongyan,Jiang, Chenran,Yin, Feng,Wang, Rui,Li, Zigang
supporting information, p. 581 - 586 (2022/01/20)
A novel amidation strategy using electrophilic sulfonium, which is soluble and stable in aqueous conditions, was developed. The sulfoniums could activate thioacid and carboxyl acid to efficiently react with amines to afford amides. This method enables applications in amidation in both aqueous media and solid-phase peptide synthesis, peptide/protein modifications, and reactive lysines of a proteome at pH 10 with activity-based protein profiling. A peptide ligand-directed labeling of the USP7-UBL2 domain was also performed using this method.
Hybrids of aurantiamide acetate and isopropylated genipin as potential anti-inflammatory agents: The design, synthesis, and biological evaluation
Wang, Hongwei,Gao, Sufan,Li, Jiaming,Ma, Xiaodong,Liu, Wandong,Qian, Shihu
, p. 797 - 808 (2020/12/03)
A novel series of hybrids designed on the basis of aurantiamide acetate and isopropylated genipin were synthesized and biologically evaluated as anti-inflammatory agents. Among them, compound 7o exhibited the best inhibitory activity against TNF-α secretion (IC50?=?16.90?μM) and was selected for further in vitro and in vivo functional study. The results demonstrated that 7o was capable of suppressing the expression of LPS-induced iNOS and COX-2, as well as reducing the production of NO at the concentration of 5?μM, which may be resulted from its regulation of NF-κB signaling and MAPK signaling. Moreover, compound 7o exhibited favorable in vivo anti-inflammatory activity with an inhibition rate of 53.32% against xylene-induced ear swelling in mice at the dose of 5?mg/kg.
Nickel-Catalyzed Multicomponent Coupling: Synthesis of α-Chiral Ketones by Reductive Hydrocarbonylation of Alkenes
Chen, Jian,Zhu, Shaolin
supporting information, p. 14089 - 14096 (2021/09/13)
A nickel-catalyzed, multicomponent regio- and enantioselective coupling via sequential hydroformylation and carbonylation from readily available starting materials has been developed. This modular multicomponent hydrofunctionalization strategy enables the straightforward reductive hydrocarbonylation of a broad range of unactivated alkenes to produce a wide variety of unsymmetrical dialkyl ketones bearing a functionalized α-stereocenter, including enantioenriched chiral α-aryl ketones and α-amino ketones. It uses chiral bisoxazoline as a ligand, silane as a reductant, chloroformate as a safe CO source, and a racemic secondary benzyl chloride or an N-hydroxyphthalimide (NHP) ester of a protected α-amino acid as the alkylation reagent. The benign nature of this process renders this method suitable for late-stage functionalization of complex molecules.
Identification and validation of selective deubiquitinase inhibitors
Auld, Douglas,Buhrlage, Sara J.,Casalena, Dominick,Chan, Wai Cheung,Dhe-Paganon, Sirano,Hu, Bin,Liu, Xiaoxi,Magin, Robert S.,Marto, Jarrod A.,Roberts, Rebekka M.,Seo, Hyuk-Soo,Varca, Anthony C.,Zhu, He
, p. 1758 - 13,1771 (2021/12/20)
Deubiquitinating enzymes (DUBs) are a class of isopeptidases that regulate ubiquitin dynamics through catalytic cleavage of ubiquitin from protein substrates and ubiquitin precursors. Despite growing interest in DUB biological function and potential as therapeutic targets, few selective small-molecule inhibitors and no approved drugs currently exist. To identify chemical scaffolds targeting specific DUBs and establish a broader framework for future inhibitor development across the gene family, we performed high-throughput screening of a chemically diverse small-molecule library against eight different DUBs, spanning three well-characterized DUB families. Promising hit compounds were validated in a series of counter-screens and orthogonal assays, as well as further assessed for selectivity across expanded panels of DUBs. Through these efforts, we have identified multiple highly selective DUB inhibitors and developed a roadmap for rapidly identifying and validating selective inhibitors of related enzymes.
On the intrinsic reactivity of highly potent trypanocidal cruzain inhibitors
Batista, Pedro Henrique Jatai,Bonatto, Vinicius,Cedron, Rodrigo,Cianni, Lorenzo,De Vita, Daniela,Franco, Caio Haddad,Montanari, Carlos A.,Moraes, Carolina Borsoi,Silva, Daniel G.,Tezuka, Daiane Y.,De Albuquerque, Sérgio,Lameira, Jer?nimo,Leit?o, Andrei
supporting information, p. 1275 - 1284 (2020/12/01)
The cysteine protease cruzipain is considered to be a validated target for therapeutic intervention in the treatment of Chagas disease. Hence, peptidomimetic cruzipain inhibitors having a reactive group (known as warhead) are subject to continuous studies
