What contributes to an effective mannose recognition domain?

• Christoph P. Sager,
• Deniz Eriş,
• Martin Smieško,
• Rachel Hevey and
• Beat Ernst

Beilstein J. Org. Chem. 2017, 13, 2584–2595, doi:10.3762/bjoc.13.255

• ) exhibits a desolvation energy of 89.6 kJ/mol due to the additional interactions to a glutamate and w2. On the other hand, w1 in the exact same binding site is the least costly among the three waters, as it forms fewer interactions and its loss can also be partially compensated by w2 (Figure 5B). Profiling

• for the formation of a homodimer of A (Figure 8B) [40]. It is believed that this dimer enables transport of the lectin from the Golgi apparatus to cell membranes [73]. Due to a dislocated glutamate in the side chain of the homodimer (Figure 8B), the affinity for calcium binding and therefore also

• /day [81]. Calcium-dependent lectins require a non-acidic environment, such as found in blood, since at lower pH the glutamate and/or aspartate side chains essential for calcium binding can become partially protonated. Instead, FimHLD forms an extensive hydrogen-bond network in a buried, rigid binding

Herpetopanone, a diterpene from Herpetosiphon aurantiacus discovered by isotope labeling

• Xinli Pan,
• Nicole Domin,
• Sebastian Schieferdecker,
• Hirokazu Kage,
• Martin Roth and
• Markus Nett

Beilstein J. Org. Chem. 2017, 13, 2458–2465, doi:10.3762/bjoc.13.242

• was obtained from the German Collection of Microorganisms and Cell Cultures (DSMZ). The bacterium was routinely cultured at 30 °C in CY (casitone 3 g/L, yeast extract 1 g/L, CaCl2·2 H2O 1 g/L, pH 6.8) or VNY liquid medium (sodium glutamate 10 g/L, yeast extract 2 g/L, MgSO4·7 H2O 2 g/L, NaH2PO4 0.10 g

Phosphonic acid: preparation and applications

• Charlotte M. Sevrain,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2017, 13, 2186–2213, doi:10.3762/bjoc.13.219

• phosphonic-carboxylic acid 93 [216] or the cyclopropylphosphonic acid 94 that was assessed as inhibitor of the glutamate metabotropic receptors [217]. The synthesis of phosphonic acid via phosphonodiamide intermediates started by the use of the nucleophilic bis(dialkylamino)chlorophosphine. This possibility

Enzymatic synthesis of glycosides: from natural O- and N-glycosides to rare C- and S-glycosides

• Jihen Ati,
• Pierre Lafite and
• Richard Daniellou

Beilstein J. Org. Chem. 2017, 13, 1857–1865, doi:10.3762/bjoc.13.180

• retention of configuration (Figure 5) as first described by Koshland [53]. However, in the case of GHs, the mechanism generally implies the intervention of two amino acid side chains, typically glutamate or aspartate, and goes through oxocarbenium ion-like transition states. Inverting GHs operate via a

Continuous-flow synthesis of highly functionalized imidazo-oxadiazoles facilitated by microfluidic extraction

• Ananda Herath and
• Nicholas D. P. Cosford

Beilstein J. Org. Chem. 2017, 13, 239–246, doi:10.3762/bjoc.13.26

• sphingosine-1-phosphate 1 (S1P1) receptor agonists [25][26][27] and metabotropic glutamate subtype 5 (mGlu5) receptor negative allosteric modulators (NAMs) [25][28][29][30]. Most synthetic efforts toward the preparation of these heterocyclic systems utilize a multistep, in-flask approach as illustrated by the

Inhibition of peptide aggregation by means of enzymatic phosphorylation

• Kristin Folmert,
• Malgorzata Broncel,
• Hans v. Berlepsch,
• Christopher H. Ullrich,
• Mary-Ann Siegert and
• Beate Koksch

Beilstein J. Org. Chem. 2016, 12, 2462–2470, doi:10.3762/bjoc.12.240

• intramolecular Coulombic repulsions between negatively charged glutamate residues and the phosphate, or in electrostatic pairing with positively charged lysine or arginine residues, resulting in the perturbation of higher ordered secondary structures [53]. The impact of electrostatics on peptide and protein

The direct oxidative diene cyclization and related reactions in natural product synthesis

• Juliane Adrian,
• Leona J. Gross and
• Christian B. W. Stark

Beilstein J. Org. Chem. 2016, 12, 2104–2123, doi:10.3762/bjoc.12.200

• by Sakai et al. together with the already known and closely related dysiherbaine [42]. Neodysiherbaine A (14) is a neurologically active compound that acts as a glutamate receptor agonist and shows epileptogenic properties. Contiguous to the isolation, the first synthesis has been carried out by the

Cyclisation mechanisms in the biosynthesis of ribosomally synthesised and post-translationally modified peptides

• Andrew W. Truman

Beilstein J. Org. Chem. 2016, 12, 1250–1268, doi:10.3762/bjoc.12.120

• precursor peptide NisA showed that dehydration involves the glutamylation of Ser and Thr side chains prior to elimination of glutamate [50]. This mechanistic proposal was established due to the observation that three NisB mutants (R786A, R826A and H961A) were able to transfer multiple glutamates to NisA

• biochemical and structural work identified that glutamate is supplied by glutamyl-tRNA, and that glutamylation and elimination steps are catalysed by distinct domains within NisB [52]. Protein homology analysis indicated that LanB-like proteins are widespread in bacteria [52], so this unusual use of an

• knotted structures, where a tail peptide is threaded through a macrolactam that is formed by the condensation of the N-terminal amino group with an asparatate or glutamate side-chain carboxylate. These are highly stable structures, and lasso peptides with a variety of biological activities have been

Synthesis, fluorescence properties and the promising cytotoxicity of pyrene–derived aminophosphonates

• Jarosław Lewkowski,
• Maria Rodriguez Moya,
• Anna Wrona-Piotrowicz,
• Janusz Zakrzewski,
• Renata Kontek and
• Gabriela Gajek

Beilstein J. Org. Chem. 2016, 12, 1229–1235, doi:10.3762/bjoc.12.117

• phosphonic analogues of phenylglycine, exhibited their herbicidal activity [10], and are used as plant growth regulators [10], agrochemical fungicides [11][12] and glutamate receptor modulators [13]. It is therefore expectable that C-pyrene derivatives may have similar or even more promising biological

Biosynthesis of α-pyrones

• Till F. Schäberle

Beilstein J. Org. Chem. 2016, 12, 571–588, doi:10.3762/bjoc.12.56

• of PpyS, docking studies of the substrates onto the catalytic cysteine were performed. The resulting model suggested that a glutamate residue, which reaches into the catalytic cavity of the respectively other homodimer, acts as a base by forming a hydrogen bond with the α-carbon of the covalently

• bound substrate (Figure 25). Indeed, the exchange of this glutamate against an alanine residue resulted in an inactive version of the protein. Further an arginine residue, which could be involved in dimerization, was mutated to an aspartate. Also this mutant lost its catalytic activity, indicating that

• to fuse two ketoacyl moieties, as exemplified by CorB and MxnB. Another mechanism is the fusion of one ketoacyl moiety with one acyl moiety, as shown for PpyS-like KSs. All evolved from FabH-type KSs, but form different clades in phylogenetic analyses. PpyS-like enzymes show the conserved glutamate

Recent applications of ring-rearrangement metathesis in organic synthesis

• Sambasivarao Kotha,
• Milind Meshram,
• Priti Khedkar,
• Shaibal Banerjee and
• Deepak Deodhar

Beilstein J. Org. Chem. 2015, 11, 1833–1864, doi:10.3762/bjoc.11.199

• the reaction of 256 with catalyst 5 in the presence of vinyl acetate (258) (Scheme 53). The RRM approach is useful to design diverse analogs of the marine toxin dysiherbaine, which displays antagonistic activity on ionotropic glutamate receptors from oxanorbornenes [54]. The report reveals the

Facile synthesis of 1-alkoxy-1H-benzo- and 7-azabenzotriazoles from peptide coupling agents, mechanistic studies, and synthetic applications

• Mahesh K. Lakshman,
• Manish K. Singh,
• Mukesh Kumar,
• Raghu Ram Chamala,
• Vijayender R. Yedulla,
• Domenick Wagner,
• Evan Leung,
• Lijia Yang,
• Asha Matin and
• Sadia Ahmad

Beilstein J. Org. Chem. 2014, 10, 1919–1932, doi:10.3762/bjoc.10.200

• reported to be promising entities in the treatment of glutamate mGluR2 receptor dysfunction-related diseases, such as neurological and psychological disorders [11]. Benzotriazole-derived compounds also have applications in materials chemistry. For example, 5-alkyl- and 5-alkanoylaminobenzotriazoles have

Isoxazolium N-ylides and 1-oxa-5-azahexa-1,3,5-trienes on the way from isoxazoles to 2H-1,3-oxazines

• Alexander F. Khlebnikov,
• Mikhail S. Novikov,
• Yelizaveta G. Gorbunova,
• Ekaterina E. Galenko,
• Kirill I. Mikhailov,
• Viktoriia V. Pakalnis and
• Margarita S. Avdontceva

Beilstein J. Org. Chem. 2014, 10, 1896–1905, doi:10.3762/bjoc.10.197

• various types of bioactivity, e.g., herbicidal [12], inhibition of cell growth and enzyme activity [13][14][15][16][17][18], inhibition of voltage-gated sodium channels [19] and metabotropic glutamate receptor-5a (hmGluR5a) [20]. Consequently, our second aim was to extend the reaction to the preparation

Application of cyclic phosphonamide reagents in the total synthesis of natural products and biologically active molecules

• Thilo Focken and
• Stephen Hanessian

Beilstein J. Org. Chem. 2014, 10, 1848–1877, doi:10.3762/bjoc.10.195

• confirming the proposed stereochemistry [49]. Glutamate metabotropic receptor agonists (2000, 2007) The metabotropic glutamate receptors (mGluRs) are members of the vast family of G-protein coupled receptors which are expressed throughout the central nervous system. They consist of at least eight sub-types

• , which are divided into three groups I–III. Through binding of glutamate 161 (Figure 9), the most abundant excitatory neurotransmitter in the mammalian central nervous system, the mGluRs are activiated and participate in the regulation of synaptic transmission and neuronal excitability through a

Automated solid-phase peptide synthesis to obtain therapeutic peptides

• Veronika Mäde,
• Sylvia Els-Heindl and
• Annette G. Beck-Sickinger

Beilstein J. Org. Chem. 2014, 10, 1197–1212, doi:10.3762/bjoc.10.118

• . Orthogonal deprotection of Dde enabled coupling of a glutamate spacer and the desired fatty acid (Figure 5) by amide-bond formation [99]. Synthesis of PEGylated conjugates (Figure 5) occurred on solid phase (for 2 kDa PEG) according to the same procedure. For PEGylation with a much larger group (20 kDa PEG

Stereocontrolled synthesis of 5-azaspiro[2.3]hexane derivatives as conformationally “frozen” analogues of L-glutamic acid

• Beatrice Bechi,
• David Amantini,
• Cristina Tintori,
• Maurizio Botta and
• Romano di Fabio

Beilstein J. Org. Chem. 2014, 10, 1114–1120, doi:10.3762/bjoc.10.110

• the identification of new potent and selective ligands of ionotropic and metabotropic glutamate receptors (GluRs). To this aim, bicycle compound Ib was designed and synthesised from D-serine as novel [2.3]-spiro analogue of L-Glu. This frozen amino acid derivative was designed to further limit the

• coupled or metabotropic glutamate receptors (mGluRs) [6][7]. To date, eight different metabotropic receptor subtypes (mGluR1–8) have been identified. Compounds that modulate the function of the mGluRs might be useful for treating a wide range of CNS disorders including schizophrenia, depression, anxiety

• (3) [11] and MGS0028 (4) [12][13]. In addition, the conformationally constrained analogues of L-Glu 6a,b, 7, 8 and 9a,b were reported [14][15][16][17][18] as either ionotropic or metabotropic glutamate receptors ligands, obtained by “freezing” the glutamate skeleton in search for subtype selective

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2013, 9, 2265–2319, doi:10.3762/bjoc.9.265

Synthesis and characterization of novel bioactive 1,2,4-oxadiazole natural product analogs bearing the N-phenylmaleimide and N-phenylsuccinimide moieties

• Catalin V. Maftei,
• Elena Fodor,
• Peter G. Jones,
• M. Heiko Franz,
• Gerhard Kelter,
• Heiner Fiebig and
• Ion Neda

Beilstein J. Org. Chem. 2013, 9, 2202–2215, doi:10.3762/bjoc.9.259

• oxadiazole core is quisqualic acid (Figure 1). This metabolite was obtained from the seeds of Quisqualis indica and Q. fructus [5][6] and is a strong agonist for AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptors and group I metabotropic glutamate receptors [7]. Furthermore, 1,2,4

Synthesis of the calcilytic ligand NPS 2143

• Henrik Johansson,
• Thomas Cailly,
• Alex Rojas Bie Thomsen,
• Hans Bräuner-Osborne and
• Daniel Sejer Pedersen

Beilstein J. Org. Chem. 2013, 9, 1383–1387, doi:10.3762/bjoc.9.154

• major classes (A, B and C) of which the rhodopsin-like class A is the largest and most diverse, and which has been well-studied and subject to drug targeting [3]. GPCR class C is much smaller and comprises only 22 known receptors including eight metabotropic glutamate (mGlu) receptors, two γ

A study on electrospray mass spectrometry of fullerenol C₆₀(OH)₂₄

• Mihaela Silion,
• Andrei Dascalu,
• Mariana Pinteala,
• Bogdan C. Simionescu and
• Cezar Ungurenasu

Beilstein J. Org. Chem. 2013, 9, 1285–1295, doi:10.3762/bjoc.9.145

• m/z 279 and [M − 12H2O + 2NH3 + 6H]6+ at m/z 158. Keywords: electrospray; fullerenol C60(OH)24; mass spectrometry; Introduction Because of their potential for chemical tunability and exciting range of biological activities as glutamate-receptor antagonists [1] and antiproliferative [2][3

Recent progress in the discovery of small molecules for the treatment of amyotrophic lateral sclerosis (ALS)

• Allison S. Limpert,
• Margrith E. Mattmann and
• Nicholas D. P. Cosford

Beilstein J. Org. Chem. 2013, 9, 717–732, doi:10.3762/bjoc.9.82

• identification of small molecules targeting specific mechanisms of neuronal pathology, including glutamate excitotoxicity, mutant protein aggregation, endoplasmic reticulum (ER) stress, loss of trophic factors, oxidative stress, or neuroinflammation. Herein, we review recent advances in the discovery and

• preclinical characterization of lead compounds that may ultimately provide novel drugs to treat patients suffering from ALS. Keywords: amyotrophic lateral sclerosis (ALS); copper/zinc (Cu-Zn) superoxide dismutase 1 (SOD1); glutamate toxicity; neurodegeneration; oxidative stress; Introduction Amyotrophic

• . Symptoms typically include muscle weakness and wasting, cramps, poor reflexes, twitching, and speech problems [1]. Few treatment options exist for this fatal disease, which typically results in death within 2–5 years of diagnosis [2]. Currently, riluzole (1), a compound which reduces glutamate

Development of peptidomimetic ligands of Pro-Leu-Gly-NH₂ as allosteric modulators of the dopamine D₂ receptor

• Swapna Bhagwanth,
• Ram K. Mishra and
• Rodney L. Johnson

Beilstein J. Org. Chem. 2013, 9, 204–214, doi:10.3762/bjoc.9.24

• recent years, the identification of allosteric modulators for GCPRs has increased significantly. The adenosine, muscarinic, chemokine, dopamine, serotonin, calcium-sensing, and metabotropic glutamate receptors are just some examples of GPCRs for which allosteric modulators have been reported [1][2]. The

A chemist and biologist talk to each other about caged neurotransmitters

• Graham C.R. Ellis-Davies

Beilstein J. Org. Chem. 2013, 9, 64–73, doi:10.3762/bjoc.9.8

• important new caged compounds were made in biology departments: (1) caged calcium [17] (molecular biology), (2) caged IP3 [5] (physiology) and carbamoylcholine [9] (biochemistry). The last of these new probes was the beginning of the development of caged neurotransmitters (e.g., glutamate, GABA, sertonin

• is thinking about using a caged transmitter in an experiment. I ask the chemist a series of simple questions about the caged compound(s); some of these questions, we discover, do not have simple answers. Glutamate is the most important neurotransmitter in the brain, as its release at nerve synapses

• transfers electrical signals between pre- and postsynaptic cells. Approximately 80% of such signaling is carried out by glutamate binding to AMPA receptors, the major post-synaptic excitatory ionotropic ion channels that bind glutamate. These receptors are blocked specifically by α-amino-3-hydroxy-5-methyl

Synthesis of conformationally restricted glutamate and glutamine derivatives from carbonylation of orthopalladated phenylglycine derivatives

• Esteban P. Urriolabeitia,
• Eduardo Laga and
• Carlos Cativiela

Beilstein J. Org. Chem. 2012, 8, 1569–1575, doi:10.3762/bjoc.8.179

• further elimination of a methyl group by 1,2-shift of the Me unit from the N atom to the Pd centre, as previously reported by Heck et al. [20]. As we have shown previously in Scheme 3, in the presence of nucleophiles the process results in the formation of conformationally restricted glutamate derivatives

• carbonylation reaction. Synthesis of methyl (1H)-isoindolin-1-one-3-carboxylates by carbonylation of phenylglycine derivatives [12]. Synthesis and NMR characterization of orthometallated complex 3. Carbonylation of 1 to afford glutamate and glutamine derivatives 2a–j. Reaction of 1 and CO in CH2Cl2 [18

Control over molecular motion using the cis–trans photoisomerization of the azo group

• Estíbaliz Merino and
• María Ribagorda

Beilstein J. Org. Chem. 2012, 8, 1071–1090, doi:10.3762/bjoc.8.119

• , azobenzene and glutamate derivative (MAG) was used as a photochromic agonist of an ionotropic glutamate receptor (iGluR) (Figure 5a) [89][90][91]. The chromophore consists of a terminal maleimide unit, which is associated covalently to the protein via a cysteine residue, a central azobenzene unit and a

• glutamate head. Only the cis form of the azobenzene allows the approach of the fragment and the interaction of glutamate with the active site of the protein. When this interaction occurs, the protein folds as a clamshell, triggering the opening of the ion channel (Figure 5b). Another recent example was