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

• TON(per cell) ≈ 20,000. The small difference between Sav_WT and the mutant Sav_Mut is explained by electrostatic repulsion of the positively charged substrate and the arginine at position 121. Another round of site-saturation mutagenesis yielded the variant Sav_R121L_N49K_A119G_T114Q_V47A (Sav_Mut2

Synthesis and photophysical studies of a multivalent photoreactive Ru^II-calix[4]arene complex bearing RGD-containing cyclopentapeptides

• Sofia Kajouj,
• Lionel Marcelis,
• Alice Mattiuzzi,
• Adrien Grassin,
• Damien Dufour,
• Pierre Van Antwerpen,
• Didier Boturyn,
• Eric Defrancq,
• Mathieu Surin,
• Julien De Winter,
• Pascal Gerbaux,
• Ivan Jabin and
• Cécile Moucheron

Beilstein J. Org. Chem. 2018, 14, 1758–1768, doi:10.3762/bjoc.14.150

• and the cyclic pentapeptides. This large variation in the distance is due to the flexibility of the linkers between the calixarene platform and the RGDfK units, together with the many possibilities of H-bonding between: (i) oxygen atoms at C=O in the linker and the hydrogen atoms of (N–H) of arginine

• of a neighboring ‘arm’; (ii) H-bonds between arginine terminal N–H and C=O of the peptide bond of phenylalanine of an adjacent cyclic pentapeptide (see Supporting Information File 1), yielding adjacent cyclic pentapeptides in close proximity for a large set of conformations. This separation between

• integrins. However, the possible H-bonding interactions between neighboring RGD units could be a drawback in view of the accessibility of the arginine groups to interact with the integrins. Photophysical properties of RuII-calixarene conjugate 9 The absorption and emission spectra of Ru-calix(RGD)4

Design and biological characterization of novel cell-penetrating peptides preferentially targeting cell nuclei and subnuclear regions

• Anja Gronewold,
• Mareike Horn and
• Ines Neundorf

Beilstein J. Org. Chem. 2018, 14, 1378–1388, doi:10.3762/bjoc.14.116

• was already determined [28]. In this case, the uptake turned out to be very low, what is in agreement with our results. The observed enhanced cellular uptake of the novel chimeric peptides might be due to an increased amount of positive charges caused by the presence of more lysine and arginine

An overview of recent advances in duplex DNA recognition by small molecules

• Sayantan Bhaduri,
• Nihar Ranjan and
• Dev P. Arya

Beilstein J. Org. Chem. 2018, 14, 1051–1086, doi:10.3762/bjoc.14.93

• hydrophobic interactions (Figure 2). Figure 2a shows that the arginine side chain of the MATα2 N-terminal arm facilitates interaction between portions of the heterodimer MATα1–MATα2 with the minor groove of the DNA substrate by forming alternate H-bond interactions [25]. The main characteristic feature of

• peptidocalix[4]arenes with arginine-rich short narrow groove binding residues on the lower rim of the calix[4]arene scaffold were reported by Soltani et al. in order to study the binding between well-matched and mismatched DNA duplexes [107]. Fluorescent titrations, ethidium bromide (EB) displacement assays

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

• which may cyclize through the formation of intramolecular disulfide bonds [39]. The most commonly used linear peptides and cyclic peptides that can be delivered inside cancer cells via endocytosis and one that smuggles into glioma tissues via transcytosis (angiopep-2) are presented below: Arginine

• -glycine-aspartic acid (RGD): A widely applied peptide carrier is the tripeptide arginine-glycine-aspartic acid (RGD) motif, which was first identified by Ruoslahti and Pierschbacher in the early 1980s [40] within fibronectin that mediates cell attachment and was known to target integrin α5β1 [41]. In

Phosphodiester models for cleavage of nucleic acids

• Satu Mikkola,
• Tuomas Lönnberg and
• Harri Lönnberg

Beilstein J. Org. Chem. 2018, 14, 803–837, doi:10.3762/bjoc.14.68

• ]. Guanidine is the side-chain functionality of arginine, an active component of the catalytic center of some nucleases, e.g., Staphylococcal nuclease [70] and topoisomerase [71]. Additionally, it is a substructure of guanine base that in hammerhead [72][73] and hairpin [74] ribozymes participates in proton

Synthesis and biological evaluation of RGD and isoDGR peptidomimetic-α-amanitin conjugates for tumor-targeting

• Lizeth Bodero,
• Paula López Rivas,
• Barbara Korsak,
• Torsten Hechler,
• Andreas Pahl,
• Christoph Müller,
• Daniela Arosio,
• Luca Pignataro,
• Cesare Gennari and
• Umberto Piarulli

Beilstein J. Org. Chem. 2018, 14, 407–415, doi:10.3762/bjoc.14.29

• ][10][11], and therefore constitutes a suitable therapeutic target in the field of SMDCs. Integrin αVβ3 recognizes endogenous ligands by the tripeptide arginine-glycine-aspartate [12] (RGD) and also by the related sequence isoaspartate-glycine-arginine (isoDGR) [13][14][15][16][17][18][19][20]. Many

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

• propargylamine 7p is not stable under the conditions, which are necessary to cleave the thioether [100][101]. Synthesis of propargylamines with basic functional groups in the side chain Very often, basic amino acids, like lysine or arginine are found in the catalytic center of enzymes. Therefore, propargylamines

• 14w have been successfully applied as inhibitors of β-glucosidases [107] and hexosamidases [108], this intramolecular Huisgen reaction could be exploited to develop novel enzyme inhibitors. In order to get access to propargylamines with the side chains of lysine, ornithine and arginine, azide 7wx

• -protected S-methylisothiourea to yield the arginine analogous propargylamine 7x in a yield of 79%. During the decomposition of the azide in the Staudinger reaction, the TMS group at the alkyne was cleaved off simultaneously. Cleavage of TMS groups with PPh3 under similar conditions has not been reported so

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

• prepare phosphohomocysteine 30 [141], the arginine mimetic 31 that was developed as a potent metallo-aminopeptidase inhibitor [142] or the aminophosphonic acid 32 [143] (Figure 10B). The mechanism of hydrolysis of diphenyl phosphonate in acidic conditions is likely different to the one occurring with

18-Hydroxydolabella-3,7-diene synthase – a diterpene synthase from Chitinophaga pinensis

• Jeroen S. Dickschat,
• Jan Rinkel,
• Patrick Rabe,
• Arman Beyraghdar Kashkooli and
• Harro J. Bouwmeester

Beilstein J. Org. Chem. 2017, 13, 1770–1780, doi:10.3762/bjoc.13.171

• diphosphate and the pyrophosphate sensor, a highly conserved arginine located 43 amino acids upstream of the NSE triad, and the RY dimer, a highly conserved motif at the C-terminus. The substrate is ionised by extrusion of diphosphate, yielding a highly reactive allyl cation that can react in a cyclisation

Chemical systems, chemical contiguity and the emergence of life

• Terrence P. Kee and
• Pierre-Alain Monnard

Beilstein J. Org. Chem. 2017, 13, 1551–1563, doi:10.3762/bjoc.13.155

• catalysis was demonstrated yet, amino acid and peptide-derivatized fatty acids (synthesized via a prebiotically plausible route) have been shown to associate with fatty acid vesicles. Vesicles with arginine-derivatized fatty acids could even electrostatically recruit RNA from the surrounding medium [70

From chemical metabolism to life: the origin of the genetic coding process

• Antoine Danchin

Beilstein J. Org. Chem. 2017, 13, 1119–1135, doi:10.3762/bjoc.13.111

• aromatic heterocycles) is based on the incorporation of amino acids in the core of nucleotide precursors. Pyrimidine nucleotide biosynthesis uses aspartate and combines together ubiquitous molecules, water, carbon dioxide, ammonium and phosphate (forming carbamoyl phosphate, also a precursor of arginine

Fluorescent carbon dots from mono- and polysaccharides: synthesis, properties and applications

• Stephen Hill and
• M. Carmen Galan

Beilstein J. Org. Chem. 2017, 13, 675–693, doi:10.3762/bjoc.13.67

• -octadecene) that could subsequently be functionalised with hydrophilic PEG-diamine, providing an amine functionality for conjugation with glucosamine, histidine, arginine and folate. The yellow/red emissive loaded-CDs were shown to be viable bioimaging probes in live cells, since their emission did not

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

Enduracididine, a rare amino acid component of peptide antibiotics: Natural products and synthesis

• Darcy J. Atkinson,
• Briar J. Naysmith,
• Daniel P. Furkert and
• Margaret A. Brimble

Beilstein J. Org. Chem. 2016, 12, 2325–2342, doi:10.3762/bjoc.12.226

• activity [45]. An approximately 10-fold reduction in activity was observed when the enduracididine residue is substituted for L-arginine [46] and almost complete loss of activity was observed when three of the four D-amino acids of this analogue are substituted for their L-counterparts [47]. Biosynthesis

• of enduracididine In 1984, a radio-labelling study was carried out to determine the biosynthesis of enduracididine (1) [48]. Arginine (18) and its precursors ornithine and citrulline, were found to be incorporated into enduracididine (1), but not histidine (19) [48]. Between the enduracidin and

• mannopeptimycin gene clusters, three pairs of enzymes were found to have high sequence homology, mmpP/endP, mppR/endR and mmpQ/endQ [49][50]. MppP is a PLP-dependent hydroxylase and catalyses the conversion of L-arginine (18) and molecular oxygen to 2-oxo-4-hydroxy-5-guanidinovaleric acid (20, Scheme 1) [51]. The

A detailed view on 1,8-cineol biosynthesis by Streptomyces clavuligerus

• Jan Rinkel,
• Patrick Rabe,
• Laura zur Horst and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2016, 12, 2317–2324, doi:10.3762/bjoc.12.225

• conserved motifs including the aspartate-rich motif (DDXXD) and the NSE triad (ND(L,I,V)XSXXXE, modified in plants to a DTE triad: DD(L,I,V)XTXXXE) [8]. Their substrates bind with the diphosphate portion to the (Mg2+)3 cluster and via hydrogen bridges to a highly conserved arginine (diphosphate sensor) and

Evidence for an iterative module in chain elongation on the azalomycin polyketide synthase

• Hui Hong,
• Yuhui Sun,
• Yongjun Zhou,
• Emily Stephens,
• Markiyan Samborskyy and
• Peter F. Leadlay

Beilstein J. Org. Chem. 2016, 12, 2164–2172, doi:10.3762/bjoc.12.206

• , requires a dedicated three-enzyme precursor pathway: L-arginine is converted by arginine monooxygenase to 4-guanidinobutyramide, 4-guanidinobutyramide hydrolase converts this to 4-guanidinobutyric acid, and the acid is then activated to 4-guanidinobutyl-CoA by 4-guanidinobutanoate:CoA ligase [35]. The

• transplanted azl cluster only contains genes for 4-guanidinobutyramide hydrolase gene and 4-guanidinobutanoate:CoA ligase [36], and the S. lividans genome contains no arginine monooxygenase, so we anticipated that heterologous azalomycin production would require added 4-guanidinobutyramide. Accordingly, S

Microwave-assisted cyclizations promoted by polyphosphoric acid esters: a general method for 1-aryl-2-iminoazacycloalkanes

• Jimena E. Díaz,
• María C. Mollo and
• Liliana R. Orelli

Beilstein J. Org. Chem. 2016, 12, 2026–2031, doi:10.3762/bjoc.12.190

• -Iminoazacycloalkanes are cyclic amidines where the formally sp2 nitrogen is exocyclic. These compounds have been described as selective inhibitors of the inducible form of human nitric oxide synthase (iNOS), which catalyzes the reaction to form nitric oxide via the oxidation of L-arginine to L-citrulline [3][4][5][6

A chiral analog of the bicyclic guanidine TBD: synthesis, structure and Brønsted base catalysis

• Mariano Goldberg,
• Denis Sartakov,
• Jan W. Bats,
• Michael Bolte and
• Michael W. Göbel

Beilstein J. Org. Chem. 2016, 12, 1870–1876, doi:10.3762/bjoc.12.176

• amino acid arginine, they play an important role in biochemistry, mainly by forming ion pairs. In addition, numerous guanidine derivatives with complex cyclic structures can be found in natural products [1]. Simple guanidines such as tetramethylguanidine have been used as strong Brønsted bases in

From supramolecular chemistry to the nucleosome: studies in biomolecular recognition

• Marcey L. Waters

Beilstein J. Org. Chem. 2016, 12, 1863–1869, doi:10.3762/bjoc.12.175

• sequence. This turned out to be an ideal problem to address using DCC, and we have now developed a number of synthetic receptors for methylated lysine and arginine that have applications as sensors for these modifications (Figure 6). Lessons learned As a child, my parents said that I “marched to my own

Mechanistic investigations on six bacterial terpene cyclases

• Patrick Rabe,
• Thomas Schmitz and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2016, 12, 1839–1850, doi:10.3762/bjoc.12.173

• -rich (DDXXD) motif near position 90 and the NSE triad (ND(L,I,V)XSXXXE) around position 230 [40][41]. Furthermore, usually 46 positions upstream of the NSE triad a highly conserved arginine (pyrophosphate sensor) and a RY dimer near the C-terminus are found that form hydrogen bonds to the diphosphate

Organic chemistry meets polymers, nanoscience, therapeutics and diagnostics

• Vincent M. Rotello

Beilstein J. Org. Chem. 2016, 12, 1638–1646, doi:10.3762/bjoc.12.161

• used to "pin" arginine-capped nanoparticles to oil droplets comprised of fatty acids. This trick worked remarkably well, providing ~150 nm nanocapsules. These capsules were unstable in serum however. Reaching back to our nanocomposite work, we were able to use bricks and mortar assembly of anionic

Superstructures with cyclodextrins: chemistry and applications III

• Gerhard Wenz and
• Eric Monflier

Beilstein J. Org. Chem. 2016, 12, 937–938, doi:10.3762/bjoc.12.91

• role. As exemplified in the following, CD chemistry has developed into a very attractive field of research. The cell-penetrating peptide octa-arginine was conjugated to methylated β-CD. The resulting biofunctionalized host was able to transport a porphyrin sulfonate into HeLa cells used in photodynamic

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

• well as FT mass spectrometry [22]. Muraymycins have a glycyl-uridine motif, which is connected via an aminopropyl linker to a urea peptide moiety consisting of L-leucine or L-hydroxyleucine, L-epicapreomycidine (a non-proteinogenic cyclic arginine derivative) and L-valine. The uridine structure is

• 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

• moiety. This led to many truncated muraymycin analogues based on the structures 7 and 8 [76]. Cbz deprotection and subsequent peptide coupling with the L-arginine-L-valine-derived urea dipeptide 9 gave various full-length muraymycin analogues 10 and 11 [76]. Some of the truncated and the full-length

Biosynthesis of α-pyrones

• Till F. Schäberle

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

• 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