Olefin metathesis catalysts embedded in β-barrel proteins: creating artificial metalloproteins for olefin metathesis

• Daniel F. Sauer,
• Johannes Schiffels,
• Takashi Hayashi,
• Ulrich Schwaneberg and
• Jun Okuda

Beilstein J. Org. Chem. 2018, 14, 2861–2871, doi:10.3762/bjoc.14.265

• movement of the catalyst with shorter spacer within the channel seems advantageous for the turnover. Additionally, a few potentially coordinating residues (glutamic acid and tyrosine) are further away from the active site when the shorter spacer is utilized [60]. Structural expansions of β-barrel proteins

Novel solid-phase strategy for the synthesis of ligand-targeted fluorescent-labelled chelating peptide conjugates as a theranostic tool for cancer

• Sagnik Sengupta,
• Mena Asha Krishnan,
• Premansh Dudhe,
• Ramesh B. Reddy,
• Bishnubasu Giri,
• Sudeshna Chattopadhyay and
• Venkatesh Chelvam

Beilstein J. Org. Chem. 2018, 14, 2665–2679, doi:10.3762/bjoc.14.244

• modified by removal of the L-glutamic acid residue to give the pteroic acid moiety (Figure 2). The binding affinity of the modified folate is relatively weaker than folic acid [41]. The targeting ligand, pteroic acid, is covalently coupled to 8-aminocaprylic acid to separate the active binding site of

• tris(tert-butoxy) protected DUPA ligand 4. Reagents and conditions: (a) Triphosgene, triethylamine, dichloromethane (DCM), −50 °C to rt; (b) L-glutamic acid γ-benzyl-α-tert-butylester hydrochloride, triethylamine, DCM, rt, overnight; (c) H2, Pd/C, CH2Cl2, 24 h, rt. Attempted synthesis of PSMA targeted

Synthesis and supramolecular self-assembly of glutamic acid-based squaramides

• Juan V. Alegre-Requena,
• Marleen Häring,
• Isaac G. Sonsona,
• Alex Abramov,
• Eugenia Marqués-López,
• Raquel P. Herrera and
• David Díaz Díaz

Beilstein J. Org. Chem. 2018, 14, 2065–2073, doi:10.3762/bjoc.14.180

• aliphatic chain and on the other side to a glutamic acid residue. The gelator bearing the free carboxylic groups showed a lower gelation capacity than its precursor diester derivative. Some selected gels were further studied by infrared spectroscopy, rheology and electron microscopy. Critical gelation

• concentrations and gel-to-sol transition temperatures were also determined for each case. In addition, the superior squaramide diester gelator was compared with an analogue triazole-based gelator in terms of critical gelation concentration, gelation kinetics and thermal phase transition. Keywords: glutamic acid

• properties of supramolecular gels [33]. Specifically, we exchanged the amide group of N-stearoyl-L-glutamic acid (1, Figure 1), a known LMW gelator [34], by its non-classical isostere [35][36] 1,4-disubstituted 1,2,3-triazole 2 (Figure 1). This approach enabled us to fine-tuning the gelation capacity and the

A self-assembled photoresponsive gel consisting of chiral nanofibers

• Lei Zou,
• Dan Han,
• Zhiyi Yuan,
• Dongdong Chang and
• Xiang Ma

Beilstein J. Org. Chem. 2018, 14, 1994–2001, doi:10.3762/bjoc.14.174

• glutamic acid skeleton, containing azobenzene as a photoresponsive group and ureidopyrimidinone (UPy) as a connection site, was designed and synthesized. The monomer is capable of forming an organogel in nonpolar organic solvents and different types of nanostructures in other solvents. The state of the gel

• -isomers of azobenzene can stack with each other via π–π interactions. Further, the acylamino group of the glutamic acid moiety at the center of the molecule also promotes this aggregation through hydrogen bonding interactions. Finally, the chirality of glutamic acid may be magnified along with the

• -dimethylaminopropyl)carbodiimide hydrochloride (EDC·HCl, 8.04 g, 0.044 mol) and 1-hydroxybenzotriazole (HOBt, 5.94 g,0.044 mol) were added to a 200 mL CH2Cl2 solution of Boc-L-glutamic acid (5 g, 0.02 mol) and 4-aminoazobenzene (7.8838 g, 0.04 mol), then the obtained mixture was stirred at room temperature for 72 h

Drug targeting to decrease cardiotoxicity – determination of the cytotoxic effect of GnRH-based conjugates containing doxorubicin, daunorubicin and methotrexate on human cardiomyocytes and endothelial cells

• Livia Polgár,
• Eszter Lajkó,
• Pál Soós,
• Orsolya Láng,
• Marilena Manea,
• Béla Merkely,
• Gábor Mező and
• László Kőhidai

Beilstein J. Org. Chem. 2018, 14, 1583–1594, doi:10.3762/bjoc.14.136

• used for amide bond formation. The difference between Dox and Dau is the lack of the primary OH group in the case of the latter one. Therefore, Dau cannot be attached to peptide carriers via an ester bond. Mtx contains a glutamic acid whose carboxyl groups are suitable for the attachment to peptides

On the design principles of peptide–drug conjugates for targeted drug delivery to the malignant tumor site

• Eirinaios I. Vrettos,
• Gábor Mező and
• Andreas G. Tzakos

Beilstein J. Org. Chem. 2018, 14, 930–954, doi:10.3762/bjoc.14.80

• in sufficient levels to pump inside the cell efficacious doses of the drug. The peptide-carrier should be constructed in such way that the conjugation with a drug or/and a fluorophore is feasible. Conjugation usually occurs on lysine, cysteine and glutamic acid [34] via orthogonal coupling or on the

Development of novel cyclic NGR peptide–daunomycin conjugates with dual targeting property

• Andrea Angelo Pierluigi Tripodi,
• Szilárd Tóth,
• Kata Nóra Enyedi,
• Gitta Schlosser,
• Gergely Szakács and
• Gábor Mező

Beilstein J. Org. Chem. 2018, 14, 911–918, doi:10.3762/bjoc.14.78

• homing devices may provide dual targeted delivery of anticancer drugs. According to literature data, one of the most stable and tumor-selective cyclic NGR-peptides is c[KNGRE]-NH2, in which the α-amino group of the N-terminal Lys is coupled to the γ-carboxyl group of the glutamic acid residue (head-to

Fluorogenic PNA probes

• Tirayut Vilaivan

Beilstein J. Org. Chem. 2018, 14, 253–281, doi:10.3762/bjoc.14.17

• (Figure 6) [40]. To ensure a close contact between the two labels, amino acids with opposite charges (typically glutamic acid and lysine) are usually placed in the vicinity of the labels. This was the practice originally used by the Boston Probe design and has been followed since by many others [40]. In

Asymmetric synthesis of propargylamines as amino acid surrogates in peptidomimetics

• Matthias Wünsch,
• David Schröder,
• Tanja Fröhr,
• Lisa Teichmann,
• Sebastian Hedwig,
• Nils Janson,
• Clara Belu,
• Jasmin Simon,
• Shari Heidemeyer,
• Philipp Holtkamp,
• Jens Rudlof,
• Lennard Klemme,
• Alessa Hinzmann,
• Beate Neumann,
• Hans-Georg Stammler and
• Norbert Sewald

Beilstein J. Org. Chem. 2017, 13, 2428–2441, doi:10.3762/bjoc.13.240

• sterically shielding protective groups have proven convenient, the trityl group turned out to be inefficient to generate a serine-analogous propargylamine. Trityl-protected imine 5m immediately decomposed, when treated with (trimethylsilyl)ethynyllithium. The preparation of glutamic acid-analogous

Posttranslational isoprenylation of tryptophan in bacteria

• Masahiro Okada,
• Tomotoshi Sugita and
• Ikuro Abe

Beilstein J. Org. Chem. 2017, 13, 338–346, doi:10.3762/bjoc.13.37

• . natto is obviously distinct from the other laboratory strains with respect to the biofilm formation. The biofilm mainly consists of the highly sticky poly-γ-glutamic acid (γ-PGA) polymer (Figure 2B), and the ComXnatto pheromone activates γ-PGA biosynthesis in B. subtilis subsp. natto at nanomolar levels

• precursors of isoprenylated peptides and proteins. The CaaX motifs are shown in red. Chemical structures of (A) surfactin A and (B) poly-γ-glutamic acid. (A) Two types of posttranslational isoprenylations of ComX variants. The modified tryptophan residues are colored blue. The isoprenyl side chains are shown

Versatile synthesis of the signaling peptide glorin

• Robert Barnett,
• Daniel Raszkowski,
• Thomas Winckler and
• Pierre Stallforth

Beilstein J. Org. Chem. 2017, 13, 247–250, doi:10.3762/bjoc.13.27

• available L-ornithine (3) and benzyloxycarbonyl-protected L-glutamic acid 5. In an improvement on previous two-step syntheses, L-ornithine δ-lactam 4 was synthesized from L-ornithine in a one-pot procedure, whereby the latter was converted into the corresponding methyl ester using trimethylsilyl chloride in

• challenge in the syntheses of glorin and analogs is the differentiation between the α- and the γ-carboxylic acid groups of L-glutamic acid for selective esterification or amidation. α-Selective functionalization was achieved via synthesis of oxazolidinone 6 from Cbz-L-glutamic acid (5) with paraformaldehyde

• previous syntheses is that ours allows for late-stage functionalization of the α-amino group of the glutamic acid moiety. This is particularly useful for the rapid generation of different α-amide analogues. Biological activity of glorin and glorinamide The bioactivities of synthetic glorin (1) and

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

• ][62][63]. Nevertheless, the change of the serine in position 23 of KFM6 to a glutamic acid does not influence the calculated propensities to form β-aggregates as the phosphorylation does (Supporting Information File 1, Figure S5). It has also been reported that not only the charge, but also 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

• domain that catalyses the hydrolysis of glutamine to glutamic acid and ammonia [95]. The McjB peptidase first removes the leader peptide to expose an N-terminal amino group, which is usually a glycine residue, although other residues have been identified at this position [97][98]. McjC then catalyses

One-pot synthesis of enantiomerically pure N-protected allylic amines from N-protected α-amino esters

• Gastón Silveira-Dorta,
• Sergio J. Álvarez-Méndez,
• Víctor S. Martín and
• José M. Padrón

Beilstein J. Org. Chem. 2016, 12, 957–962, doi:10.3762/bjoc.12.94

• , and N-Ac and N-Boc glutamic acid dialkyl esters, this time using a stabilized phosphonate ester [18]. This strategy was used later on in the synthesis of aminopeptidase A inhibitors [19]. Similarly, N-methylproline methyl ester was reacted in a similar one-pot fashion during the synthesis of nine

Muraymycin nucleoside-peptide antibiotics: uridine-derived natural products as lead structures for the development of novel antibacterial agents

• Daniel Wiegmann,
• Stefan Koppermann,
• Marius Wirth,
• Giuliana Niro,
• Kristin Leyerer and
• Christian Ducho

Beilstein J. Org. Chem. 2016, 12, 769–795, doi:10.3762/bjoc.12.77

• between F288 and glutamic acid 287 (E287) with the peptide motif arginine-tryptophan-x-x-tryptophan (RWxxW, x represents an arbitrary amino acid) was found. Mutants F288L and E287A showed reduced or no detectable enzyme inhibition, thus indicating a secondary binding site for potential MraY inhibitors

A novel and widespread class of ketosynthase is responsible for the head-to-head condensation of two acyl moieties in bacterial pyrone biosynthesis

• Darko Kresovic,
• Florence Schempp,
• Zakaria Cheikh-Ali and
• Helge B. Bode

Beilstein J. Org. Chem. 2015, 11, 1412–1417, doi:10.3762/bjoc.11.152

• condensation of two long-chain fatty acid thioesters, similar to the proposed mechanism of PpyS (Scheme 1). The dimeric structure of OleA revealed a unique feature that has not been described previously for other KS, in which one glutamic acid residue reaches inside the binding pocket of the adjacent monomer

• PpyS is capable of harboring both molecules. Similar to the OleA model, the PpyS model suggests glutamic acid E105 acting as a base by forming a hydrogen bond with the α-carbon of both covalently bound substrates. To confirm this hypothesis, a E105A derivative of PpyS was produced in E. coli resulting

• crystal structure of MxnB has been solved [26]. Unlike PpyS, the proposed mechanism does not show a similar glutamic acid to be involved. A multiple sequence alignment of MxnB, CorB, PpyS and other KS (Figure S9, Supporting Information File 1) reveals that in both MxnB and CorB KS E105 in PpyS is replaced

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

• ) [57]. Pellicciari and co-workers also reported on the synthesis of other constrained bioisosteres of L-glutamic acid, such as PCCG-4 (163) (Figure 9) [124]. To this end, phosphonocyclopropylamino acid 21 was designed as an analogue to 163 by replacing a carboxylic acid with a phosphonic acid moiety

Design, automated synthesis and immunological evaluation of NOD2-ligand–antigen conjugates

• Marian M. J. H. P. Willems,
• Gijs G. Zom,
• Nico Meeuwenoord,
• Ferry A. Ossendorp,
• Herman S. Overkleeft,
• Gijsbert A. van der Marel,
• Jeroen D. C. Codée and
• Dmitri V. Filippov

Beilstein J. Org. Chem. 2014, 10, 1445–1453, doi:10.3762/bjoc.10.148

• -azidopropanol spacers at the anomeric center of MurNAc in conjugate 2 and 3 remain unmodified. In conjugates 4 and 5 on the other hand the 3-azidopropanol is functionalized with glutamic acid allowing conjugation to the antigenic peptide at the N-terminus for conjugate 4 and at the C-terminus for conjugate 5

• MurNAc 10 in 93% yield [39][40]. Fully protected MDP 14 was obtained by condensation of acid 10 and dipeptide 13. To this end, Fmoc-protected tert-butyl glutamic acid 11 was reacted with di-tert-butyl dicarbonate and transformed into 12 [41]. In a one-pot procedure compound 12 was deprotected with DBU

• with the reduction of the azide in compound 14 with PMe3 and subsequently the primary amine and Fmoc protected glutamic acid allyl ester were condensed under influence of HATU and DiPEA to give the orthogonally protected compound 15 in 57% yield. To make 15 suitable for SPPS, the allyl protective group

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

• respective protecting groups are illustrated. Blue arrows indicate basic and red/purple arrows indicate acidic conditions. Dashed boxes stress the COOH-side-chain protecting group of glutamic acid exemplarily, used in each strategy. “Drugability” attributes of peptide therapeutics compared with small

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

• -glutamic acid (L-Glu, 1) is of particular importance since it is the primary excitatory neurotransmitter in the mammalian central nervous system (CNS) and plays a critical role in a wide range of disorders like schizophrenia, depression, neurodegenerative diseases such as Parkinson’s and Alzheimer’s and in

• ; Introduction L-Glutamic acid (L-Glu) is the primary excitatory neurotransmitter in the mammalian central nervous system (CNS) playing a critical role in the learning and memory process [1][2][3]. L-Glu receptors can be subdivided in ionotropic receptors (NMDA, AMPA and kainite receptors) [4][5] and G-protein

• 26a and 26c. The final cleavage of the Boc protecting group was carried out in the presence of formic acid at room temperature, affording the target amino acid derivatives 27a and 27c (Scheme 4). Conclusion In conclusion, two complex bridged analogues 27a,c of glutamic acid were synthesized. Starting

Olefin cross metathesis based de novo synthesis of a partially protected L-amicetose and a fully protected L-cinerulose derivative

• Bernd Schmidt and
• Sylvia Hauke

Beilstein J. Org. Chem. 2014, 10, 1023–1031, doi:10.3762/bjoc.10.102

• perdeuteration of an alkynoate derived from L-threonine (giving a 2,2,3,3-tetradeuterated amicetose) [26], enantioselective hydroboration of hetero Diels–Alder adducts [27], stereoconservative diazotation of L-glutamic acid [28][29], diastereoselective addition of methylmagnesium bromide to enantiopure 2

A novel family of (1-aminoalkyl)(trifluoromethyl)- and -(difluoromethyl)phosphinic acids – analogues of α-amino acids

• Natalia V. Pavlenko,
• Tatiana I. Oos,
• Yurii L. Yagupolskii,
• Igor I. Gerus,
• Uwe Doeller and
• Lothar Willms

Beilstein J. Org. Chem. 2014, 10, 722–731, doi:10.3762/bjoc.10.66

• , bearing side chain C–F linkages are well documented in a review [10]. The isolation of phosphinothricin, a naturally occurring phosphorus analogue of glutamic acid and the discovery of its antibiotic, fungicidal and herbicidal properties [11] has led to an increased activity in the study of

Concise, stereodivergent and highly stereoselective synthesis of cis- and trans-2-substituted 3-hydroxypiperidines – development of a phosphite-driven cyclodehydration

• Peter H. Huy,
• Julia C. Westphal and
• Ari M. P. Koskinen

Beilstein J. Org. Chem. 2014, 10, 369–383, doi:10.3762/bjoc.10.35

• side chain carboxyl function with acetyl chloride in MeOH [70][71][72]. Neutralization of the reaction mixture with K2CO3 and reductive benzylation [73] in one-pot then delivered the benzyl amines 8e and 8f. While glutamic acid showed selective mono esterification after 3 h at room temperature, the

• Schotten–Baumann conditions [62][63]. Thus, K2CO3 (→ pH = 10) as the base prevented saponification of the side chain methyl ester functions (as observed with hydroxide salts). Nevertheless, in the acylation of the glutamic acid derivative 8e the corresponding pyroglutamic acid derivative 2g resulting from

Towards stereochemical control: A short formal enantioselective total synthesis of pumiliotoxins 251D and 237A

• Jie Zhang,
• Hong-Kui Zhang and
• Pei-Qiang Huang

Beilstein J. Org. Chem. 2013, 9, 2358–2366, doi:10.3762/bjoc.9.271

• -hydroxyglutarimide 19 (prepared from (R)-glutamic acid in 69% overall yield over 4 steps [47]) in a yield of 95%. Successive treatment of imide 14 with 3-butenylmagnesium bromide (CH2Cl2, −20 °C, 3 h) and the resulting hemi-aminal with Et3SiH/BF3·Et2O (CH2Cl2, −78 °C, 2 h, then −20 °C, 2 h) gave a diastereomeric

C–C Bond formation catalyzed by natural gelatin and collagen proteins

• Dennis Kühbeck,
• Basab Bijayi Dhar,
• Eva-Maria Schön,
• Carlos Cativiela,
• Vicente Gotor-Fernández and
• David Díaz Díaz

Beilstein J. Org. Chem. 2013, 9, 1111–1118, doi:10.3762/bjoc.9.123

• composition of gelatin in terms of its amino acids content has been reported in several publications (arginine, glutamic acid, alanine, glycine, proline and hydroxyproline are the most abundant amino acids (ca. 10–25%)) [1], which makes the protein itself suitable for catalytic studies. The Henry (nitroaldol