Activity assays of NnlA homologs suggest the natural product N-nitroglycine is degraded by diverse bacteria

• Kara A. Strickland,
• Brenda Martinez Rodriguez,
• Ashley A. Holland,
• Shelby Wagner,
• Michelle Luna-Alva,
• David E. Graham and
• Jonathan D. Caranto

Beilstein J. Org. Chem. 2024, 20, 830–840, doi:10.3762/bjoc.20.75

• voltage of 4,500 V and a fragmentation voltage of 175 V. To monitor NNG, 2-NAE, and glyoxylate, extracted ion chromatograms were obtained at m/z 119.0, 105.0, and 73.0, respectively. Ammonium concentrations were determined using a glutamate dehydrogenase assay (Sigma-Aldrich) kit using the manufacturer’s

Methodology for awakening the potential secondary metabolic capacity in actinomycetes

• Shun Saito and
• Midori A. Arai

Beilstein J. Org. Chem. 2024, 20, 753–766, doi:10.3762/bjoc.20.69

• production of antibiotics such as actinorhodin (ACT, 8), undecylprodigiosin (RED, 21), and calcium-dependent antibiotic (CDA, 22) in Streptomyces coelicolor M145 (Figure 3b). Chen et al. and Shu et al. reported that under stress associated with high concentrations of glutamate, AfsQ1/Q2 is important not only

Substrate specificity of a ketosynthase domain involved in bacillaene biosynthesis

• Zhiyong Yin and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2024, 20, 734–740, doi:10.3762/bjoc.20.67

• glutamate decarboxylase, and incubated with BaeJ-KS2. Substrate binding was demonstrated through 13C NMR analysis of the products against the background of various control experiments. Keywords: bacillaene; biosynthesis; enzyme mechanisms; isotopes; trans-AT polyketide synthases; Introduction Polyketides

• , to investigate the function of the KS domain BaeJ-KS2 the synthesis of 13C-labelled (S)-11 as a mimic of the intermediate bound to the ACP of module 3 was performed. It was planned to introduce the 13C-labelling from (5-13C)glutamate into the γ-aminobutyrate portion of (S)-11. For this purpose, the

• gene coding for the glutamate decarboxylase from Escherichia coli K12 (accession no. AAA23833) was cloned through homologous recombination in yeast into the expression vector pYE-Express [26]. Heterologous expression and purification of the recombinant enzyme (Figure S1, Supporting Information File 1

Pseudallenes A and B, new sulfur-containing ovalicin sesquiterpenoid derivatives with antimicrobial activity from the deep-sea cold seep sediment-derived fungus Pseudallescheria boydii CS-793

• Zhen Ying,
• Xiao-Ming Li,
• Sui-Qun Yang,
• Hong-Lei Li,
• Xin Li,
• Bin-Gui Wang and
• Ling-Hong Meng

Beilstein J. Org. Chem. 2024, 20, 470–478, doi:10.3762/bjoc.20.42

• chromatography (TLC) was performed with precoated Si gel GF254 plates (Merck, Darmstadt, Germany). Solvents used for extraction and purification were distilled prior to use. Peptone from yeast extract was purchased from Sigma-Aldrich. Rice, monosodium glutamate, and corn steep liquor were purchased from China

• ), monosodium glutamate (0.1 g/flask), and naturally sourced and filtered seawater (acquired from the Huiquan Gulf of the Yellow Sea near the campus of IOCAS, 100 mL/flask) were autoclaved at 120 °C for 20 min before inoculation. The fresh mycelia of the fungus P. boydii CS-793 were incubated in a shaker on PDB

Facile and diastereoselective arylation of the privileged 1,4-dihydroisoquinolin-3(2H)-one scaffold

• Dmitry Dar’in,
• Grigory Kantin,
• Alexander Bunev and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2022, 18, 1070–1078, doi:10.3762/bjoc.18.109

• receptors 1 [3], AChE and BACE-1 inhibitor 2 [4], inhibitor of oncogenic p53-MDM2 protein–protein interaction 3 [5], positive allosteric modulator of ionotropic glutamate receptor NMDA-1 4 [6], insulin-like growth factor 1 receptor inhibitor 5 [7], and metabotropic glutamate receptor 7 modulator 6 [8

BINOL as a chiral element in mechanically interlocked molecules

• Matthias Krajnc and
• Jochen Niemeyer

Beilstein J. Org. Chem. 2022, 18, 508–523, doi:10.3762/bjoc.18.53

• ) and two NH donors (on the macrocycle). For the anion-recognition experiments, the binding of selected dicarboxylate anions ((S/R)-glutamate, fumarate, and maleate) was investigated by fluorescence titrations. This revealed an impressive chiral discrimination towards (S)-Glu2− with a selectivity of K(S

Regioselective synthesis of methyl 5-(N-Boc-cycloaminyl)-1,2-oxazole-4-carboxylates as new amino acid-like building blocks

• Jolita Bruzgulienė,
• Greta Račkauskienė,
• Aurimas Bieliauskas,
• Vaida Milišiūnaitė,
• Miglė Dagilienė,
• Gita Matulevičiūtė,
• Vytas Martynaitis,
• Sonata Krikštolaitytė,
• Frank A. Sløk and
• Algirdas Šačkus

Beilstein J. Org. Chem. 2022, 18, 102–109, doi:10.3762/bjoc.18.11

• muscimol (I) and ibotenic acid (II) (Figure 1) have been isolated from several fungal species and are active on the γ-aminobutyric acid (GABA) and glutamate receptors of the central nervous system (CNS), respectively [8][9]. Various unnatural amino acids bearing a 1,2-oxazole moiety, such as

• nonproteinogenic α-amino acids, have been used as excitatory amino acid receptor agonists [10][11][12][13]. For example, (S)-AMPA (III) and (S)-ACPA (IV) are specific agonists of an AMPA receptor that mimic the effects of the neurotransmitter glutamate [14][15][16]. Unnatural heteroarene amino acids have also been

Enantioenriched α-substituted glutamates/pyroglutamates via enantioselective cyclopropenimine-catalyzed Michael addition of amino ester imines

• Zara M. Seibel,
• Jeffrey S. Bandar and
• Tristan H. Lambert

Beilstein J. Org. Chem. 2021, 17, 2077–2084, doi:10.3762/bjoc.17.134

• -substituted glutamate derivatives is via the Michael addition of α-amino ester enolates to acrylate acceptors. These products can also be easily converted to pyroglutamates by lactamization [28][29][30]. Although the use of substituted amino ester derivatives for the enantioselective α-alkylation has been

• enolate geometry and N–H vs O–H binding). From this transition state, addition of the enolate to the acrylate followed by rapid proton transfer would lead to the glutamate derivative 10 (path a, red dashed line). A competing pathway involving bond formation between the acrylate α-carbon and the imine

• chemistry remains quite sensitive to structural modifications, and thus there remains significant room for further development. Nevertheless, this work provides a convenient means to access a variety of these important structural motifs. Strategy for the synthesis of glutamate and pyroglutamate derivatives

Menthyl esterification allows chiral resolution for the synthesis of artificial glutamate analogs

• Kenji Morokuma,
• Shuntaro Tsukamoto,
• Kyosuke Mori,
• Kei Miyako,
• Ryuichi Sakai,
• Raku Irie and
• Masato Oikawa

Beilstein J. Org. Chem. 2021, 17, 540–550, doi:10.3762/bjoc.17.48

• enantiospecific synthesis of two artificial glutamate analogs designed based on IKM-159, an antagonist selective to the AMPA-type ionotropic glutamate receptor. The synthesis features the chiral resolution of the carboxylic acid intermediate by the esterification with ʟ-menthol, followed by a configurational

• the activity is controlled by the ring C. Keywords: chiral resolution; configurational analysis; glutamate; metathesis; neuroactivity; Introduction The ionotropic glutamate receptor (iGluR) mediates the majority of the excitatory neurotransmission in the mammalian central nervous system (CNS) and

• plays an important role in higher brain functions, such as learning and memory [1]. Previously, we have synthetically developed (2R)-IKM-159 (1) as an artificial glutamate analog that is selectively antagonistic to AMPA-type iGluR (Figure 1) [2][3]. From a series of these studies (see 1, 2, and 5 in

Synthetic strategies of phosphonodepsipeptides

• Jiaxi Xu

Beilstein J. Org. Chem. 2021, 17, 461–484, doi:10.3762/bjoc.17.41

• , indicating that this strategy was not suitable for the synthesis of γ-phosphonodepsipeptides (Scheme 13) [28]. Folylpolyglutamate synthetase catalyzes an ATP-dependent ligation reaction. The reaction results in the synthesis of poly(γ-glutamate) metabolites of folates and some antifolates. Three γ

Biochemistry of fluoroprolines: the prospect of making fluorine a bioelement

• Vladimir Kubyshkin,
• Rebecca Davis and
• Nediljko Budisa

Beilstein J. Org. Chem. 2021, 17, 439–460, doi:10.3762/bjoc.17.40

• pathways for proline biosynthesis involve the synthesis from either glutamate or ornithine [61]. Both sources of amino acids are derived from the core metabolic processes. The connection to the central metabolism makes it difficult to make interventions in the production of proline in the cells. For

• example, in order to create an organism that fully lacks the ability to synthesize proline (which is called a proline auxotrophic strain), one should delete or inactivate genes involved in the metabolism of ornithine and glutamate. As the result, this may lead to an unnecessary accumulation of other amino

• acids and their metabolic derivatives, which may impact cellular homeostasis. In addition, proline metabolism is related to stress response and scavenging of reactive oxygen species in many organisms [62]. In E. coli, the main path for proline synthesis starts from glutamate, which is phosphorylated by

¹⁹F NMR as a tool in chemical biology

• Diana Gimenez,
• Aoife Phelan,
• Cormac D. Murphy and
• Steven L. Cobb

Beilstein J. Org. Chem. 2021, 17, 293–318, doi:10.3762/bjoc.17.28

• are being investigated that enable the enzymatic post-translational modification of non-nucleophilic residues, such as glutamate [31]. As recently demonstrated by Kojima and co-workers, recombinant protein transglutaminase (TGase) could be used to catalyse the chemical replacement of the γ

The preparation and properties of 1,1-difluorocyclopropane derivatives

• Kymbat S. Adekenova,
• Peter B. Wyatt and
• Sergazy M. Adekenov

Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25

Molecular basis for protein–protein interactions

• Brandon Charles Seychell and
• Tobias Beck

Beilstein J. Org. Chem. 2021, 17, 1–10, doi:10.3762/bjoc.17.1

• hydrophobic residues, such as leucine, phenylalanine, tryptophan, and methionine, as well as polar residues, such as aspartate, glutamate, histidine, and arginine, tend to be part of bifurcated interactions. On the other hand, glutamine and lysine were the only amino acids that tend to not take part in such

Selected peptide-based fluorescent probes for biological applications

• Debabrata Maity

Beilstein J. Org. Chem. 2020, 16, 2971–2982, doi:10.3762/bjoc.16.247

• recognition; peptide-based; Introduction Molecular recognition involving amino acids or peptides are important factors in biochemical and medicinal processes [1][2][3]. Amino acids work as biosynthetic building blocks or as signaling molecules. For example, the well-known neurotransmitters glutamate and γ

• a bound glutamate molecule [4]. Peptides often work as signaling molecules or hormones, such as small neuropetide endorphins, produced by the central nervous system to relieve stress or enhance pleasure. They produce signaling cascades in the brain by interacting with opiate receptors. Sometimes

NMR Spectroscopy of supramolecular chemistry on protein surfaces

• Peter Bayer,
• Anja Matena and
• Christine Beuck

Beilstein J. Org. Chem. 2020, 16, 2505–2522, doi:10.3762/bjoc.16.203

• guanidinocarbonylpyrrole (GCP)-based ligands [41]. GCP mimics the natural amino acid arginine binding to the carboxylate side chains of aspartate (Asp) and glutamate (Glu). The GCP unit provides an extended hydrogen bonding/salt bridge interface, which leads to better binding compared to its natural counterpart. The

• applied in this context yet. The specific labeling of glutamate is more challenging because this amino acid is easily metabolized into several other amino acid types. However, the specific incorporation of 15N-labeled glutamate in non-auxotrophic E. coli strains is possible using inhibitors for the

• metabolic enzymes converting glutamate [111]. The bacteria are grown in a modified M9 minimal medium containing the labeled amino acid, all others in unlabeled form, and the corresponding metabolic pathway inhibitors. To our knowledge, this method has not been applied to study the binding of ligands that

Automated high-content imaging for cellular uptake, from the Schmuck cation to the latest cyclic oligochalcogenides

• Rémi Martinent,
• Javier López-Andarias,
• Dimitri Moreau,
• Yangyang Cheng,
• Naomi Sakai and
• Stefan Matile

Beilstein J. Org. Chem. 2020, 16, 2007–2016, doi:10.3762/bjoc.16.167

• for the thiol-mediated uptake, beginning with a dynamic covalent disulfide exchange with exofacial thiols, followed by either endocytosis or the direct crossing of membranes into cytosols through successive thiolate–disulfide exchange reactions or micellar pores (Figure 5b) [61]. Anionic glutamate was

A toolbox of molecular photoswitches to modulate the CXCR3 chemokine receptor with light

• Xavier Gómez-Santacana,
• Sabrina M. de Munnik,
• Tamara A. M. Mocking,
• Niels J. Hauwert,
• Shanliang Sun,
• Prashanna Vijayachandran,
• Iwan J. P. de Esch,
• Henry F. Vischer,
• Maikel Wijtmans and
• Rob Leurs

Beilstein J. Org. Chem. 2019, 15, 2509–2523, doi:10.3762/bjoc.15.244

• explored on GPCRs targeted endogenously by small molecules [3][4][11][16][17][18][19][20], small peptides [5][13] and larger peptides [7][21][22]. Most of the targeted GPCRs belong to the three rhodopsin-, secretin- and glutamate-like subfamilies and involve GPCRs that endogenously bind small-molecule

Synthesis and biological evaluation of truncated derivatives of abyssomicin C as antibacterial agents

• Leticia Monjas,
• Peter Fodran,
• Johanna Kollback,
• Carlo Cassani,
• Thomas Olsson,
• Maja Genheden,
• D. G. Joakim Larsson and
• Carl-Johan Wallentin

Beilstein J. Org. Chem. 2019, 15, 1468–1474, doi:10.3762/bjoc.15.147

• covalent inhibitor of 4-amino-4-deoxychorismate (ADC) synthase, which is the enzyme that catalyzes the conversion of chorismate and glutamine into ADC and glutamate, the first step in the biosynthesis of p-aminobenzoic acid (PABA) in bacteria [6]. Specifically, AbC binds via a Michael addition between a

Photochemical generation of the 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) radical from caged nitroxides by near-infrared two-photon irradiation and its cytocidal effect on lung cancer cells

• Ayato Yamada,
• Manabu Abe,
• Yoshinobu Nishimura,
• Shoji Ishizaka,
• Masashi Namba,
• Taku Nakashima,
• Kiyofumi Shimoji and
• Noboru Hattori

Beilstein J. Org. Chem. 2019, 15, 863–873, doi:10.3762/bjoc.15.84

• -responsive photo-labile protecting group [56][57][58] with simple cyclic stilbene structures such as 2-(4-nitrophenyl)benzofuran (NPBF) that absorb in the NIR region of 710–760 nm for the uncaging of bioactive substances such as glutamate and Ca2+ [59][60][61][62][63][64]. Herein, we report the synthesis of

Syntheses and chemical properties of β-nicotinamide riboside and its analogues and derivatives

• Mikhail V. Makarov and
• Marie E. Migaud

Beilstein J. Org. Chem. 2019, 15, 401–430, doi:10.3762/bjoc.15.36

Synthesis of nonracemic hydroxyglutamic acids

• Dorota G. Piotrowska,
• Iwona E. Głowacka,
• Andrzej E. Wróblewski and
• Liwia Lubowiecka

Beilstein J. Org. Chem. 2019, 15, 236–255, doi:10.3762/bjoc.15.22

• pool; glutamate analogues; Introduction L-Glutamic acid (1, Figure 1) plays an important role in the biosynthesis of purine and pyrimidine nucleobases [1]. It also takes part in metabolic transformation to L-glutamine by L-glutamate synthetase (GS) which is crucial for cell maintenance. In neoplastic

• ]. Several derivatives of L-glutamic acid functioning as anticancer agents have been reported [4]. But primarily L-glutamic acid is known as the major excitatory neurotransmitter in central nervous system which acts by binding to glutamate receptors [5][6][7]. However, these interactions are linked to

• additional substituents, tuning the conformational flexibility of analogues and introducing groups capable of hydrogen bonding. Crystallographic data obtained for glutamate receptors [13][14][15] showed complex set of atoms interacting electrostatically and through hydrogen bonds and the conclusions from

Volatiles from three genome sequenced fungi from the genus Aspergillus

• Jeroen S. Dickschat,
• Ersin Celik and
• Nelson L. Brock

Beilstein J. Org. Chem. 2018, 14, 900–910, doi:10.3762/bjoc.14.77

• motif that is typical for class II TSs (312DADD) and the C-terminal domain exhibits an aspartate-rich motif DDXXD, in this case with two of the usually found asparate residues exchanged by glutamate, and an NSE triad, a motif with highly conserved Asn, Ser and Glu residues, for Mg2+ binding as in class

Latest development in the synthesis of ursodeoxycholic acid (UDCA): a critical review

• Fabio Tonin and
• Isabel W. C. E. Arends

Beilstein J. Org. Chem. 2018, 14, 470–483, doi:10.3762/bjoc.14.33

• most used enzymes for the cofactor regeneration are glucose dehydrogenase (glucose to glucuronic acid), lactate dehydrogenase (pyruvate to lactate), glutamate dehydrogenase (α-ketoglutarate to glutamate) and formate dehydrogenase (formate to CO2). In particular, the last enzyme is interesting because

Stereochemical outcomes of C–F activation reactions of benzyl fluoride

• Neil S. Keddie,
• Pier Alexandre Champagne,
• Justine Desroches,
• Jean-François Paquin and
• David O'Hagan

Beilstein J. Org. Chem. 2018, 14, 106–113, doi:10.3762/bjoc.14.6

• an enantiopure isotopomer of benzyl fluoride to identify whether the reaction conditions favour a dissociative (SN1) or associative (SN2) pathway. [2H]-Isotopomer ratios in the reactions were assayed using the Courtieu 2H NMR method in a chiral liquid crystal (poly-γ-benzyl-L-glutamate) matrix and

• with the electric field gradients associated with the orientated media, creating anisotropy and resolving into two sets of doublets. If there is sufficient resolution between these quadrupolar couplings, then the enantiomeric ratio can be recorded. We have used poly-γ-benzyl-L-glutamate (PBLG