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

• activity even in the presence of millimolar concentrations of 2-NAE (Table S4, Supporting Information File 1). This observation suggests that binding in the substrate pocket is dependent on an electrostatic interaction with the NNG α-carboxylate, most likely from a lysine, arginine, histidine side chain or

• the N-terminus. An alignment of orthologous protein sequences reveals several conserved basic residues (Figure S4, Supporting Information File 1). The only conserved histidine residue is H73, which has been assigned as a heme ligand. Conserved arginine and lysine residues are colored magenta in the Vs

New variochelins from soil-isolated Variovorax sp. H002

• Jabal Rahmat Haedar,
• Aya Yoshimura and
• Toshiyuki Wakimoto

Beilstein J. Org. Chem. 2024, 20, 692–700, doi:10.3762/bjoc.20.63

• serine (Ser), a β-hydroxyaspartic acid (Hya), and a unique γ-amino acid biosynthetically originating from an arginine and a methyl malonate (4-amino-7-guanidino-3-hydroxy-2-methylheptanoic acid), with the amino group acylated by a saturated fatty acid. Subsequent HMBC and MS/MS analyses indicated that

• : epimerization domain, TE: thioesterase domain, KS: ketosynthase domain, AT: acyl transferase domain, KR: ketoreductase domain, TauD: taurine dioxygenase domain. Substrate specificity of A and KS domains is presented at the top of each module (FA: fatty acyl, Arg: arginine, MM: methyl malonyl, Asp: aspartic acid

Discrimination of β-cyclodextrin/hazelnut (Corylus avellana L.) oil/flavonoid glycoside and flavonolignan ternary complexes by Fourier-transform infrared spectroscopy coupled with principal component analysis

• Nicoleta G. Hădărugă,
• Gabriela Popescu,
• Dina Gligor (Pane),
• Cristina L. Mitroi,
• Sorin M. Stanciu and
• Daniel Ioan Hădărugă

Beilstein J. Org. Chem. 2023, 19, 380–398, doi:10.3762/bjoc.19.30

• , cyclosporine A and polyvinyl alcohol, ketoprofen and phospholipids, dihydroartemisinin and lecithin, cefixime and ʟ-arginine, flurbiprofen and naproxen/ketoprofen/ethenzamide [50][51][52][53][54][55][56][57][58][59]. Fourier-transform infrared spectroscopy (FTIR) is a very fast, nondestructive and cheap method

Sinensiols H–J, three new lignan derivatives from Selaginella sinensis (Desv.) Spring

• Qinfeng Zhu,
• Beibei Gao,
• Qian Chen,
• Tiantian Luo,
• Guobo Xu and
• Shanggao Liao

Beilstein J. Org. Chem. 2022, 18, 1410–1415, doi:10.3762/bjoc.18.146

• physiochemical properties and spectral data with those reported in the literature. Biological activity The isolated compounds were screened for their inhibitory effects on the LPS-induced NO production in RAW 264.7 macrophages. NG-Monomethyl-ʟ-arginine monoacetate salt (ʟ-NMMA, Sigma) was used as the positive

Make or break: the thermodynamic equilibrium of polyphosphate kinase-catalysed reactions

• Michael Keppler,
• Sandra Moser,
• Henning J. Jessen,
• Christoph Held and
• Jennifer N. Andexer

Beilstein J. Org. Chem. 2022, 18, 1278–1288, doi:10.3762/bjoc.18.134

• fractions [5][10][15][16]. Based on the crystal structures of three PPK2-III, the coordination of polyP and ADP by positively charged amino acids (lysine and arginine) has been suggested [16][17]. Two magnesium ions are held in place by two conserved aspartate residues that further coordinate the polyP and

Identification of the new prenyltransferase Ubi-297 from marine bacteria and elucidation of its substrate specificity

• Jamshid Amiri Moghaddam,
• Huijuan Guo,
• Karsten Willing,
• Thomas Wichard and
• Christine Beemelmanns

Beilstein J. Org. Chem. 2022, 18, 722–731, doi:10.3762/bjoc.18.72

• aromatic Ptases such as MenA (DXXDXXXXXD). While most UbiA Ptases, such as of E. coli UbiA (C5A133) and human COQ2 (Q96H96), carry a basic arginine residue within the central cavity and which is proposed to bind the aromatic substrate (e.g., 4-hydroxybenzoate), UbiA-297 and other G2-Ptases harbor instead a

• tyrosine (Tyr-56) residue, which likely fulfills a similar coordinative function. Furthermore, a conserved arginine residue (UbiA-297 R145) was detectable, which was located in the neighboring α-helix (R145) and in proximity to the binding motif, and was hypothesized to be involved in the coordination

• and A. machipongonensis sp. PR1 were synthesized. To gain more insights into the binding properties of UbiA-297 and the functional role of the conserved arginine moiety (R145), an additional point-mutated ubiA-297 (R145A) version was synthesized codon-optimized for expression in E. coli. Synthesized

Anomeric 1,2,3-triazole-linked sialic acid derivatives show selective inhibition towards a bacterial neuraminidase over a trypanosome trans-sialidase

• Peterson de Andrade,
• Sanaz Ahmadipour and
• Robert A. Field

Beilstein J. Org. Chem. 2022, 18, 208–216, doi:10.3762/bjoc.18.24

• virus neuraminidase is due to a strong electrostatic interaction between the phosphonate group and the arginine pocket in the active site [40]. Conclusion A small series of anomeric 1,2,3-triazole-linked sialic acid derivatives was synthesised in good yields and high purity via CuAAC click chemistry and

Synthesis and bioactivity of pyrrole-conjugated phosphopeptides

• Qiuxin Zhang,
• Weiyi Tan and
• Bing Xu

Beilstein J. Org. Chem. 2022, 18, 159–166, doi:10.3762/bjoc.18.17

• . Switching the ᴅ-phosphoserine in 4a and 4b by ʟ-phosphoserine (pS), creates 5a and 5b. ᴅ-Trialanine replaces triglycine in 2f–h to produce 6a–c, which should resist to proteases, such as polyglycine hydrolases [73], which are known to cleave at the glycine–glycine site. The addition of an arginine residue

• motif and one to three pyrrole motifs at the N-terminal, hardly inhibit the HeLa cells. Compound 7, formed by the introduction of a ᴅ-arginine residue into 2a, exhibits similar cytotoxicity as that of 2a. 8a and 8b, formed by replacing the ff motif in 2d and 2e with l4, exhibit slight and little

Chemical approaches to discover the full potential of peptide nucleic acids in biomedical applications

• Nikita Brodyagin,
• Martins Katkevics,
• Venubabu Kotikam,
• Christopher A. Ryan and
• Eriks Rozners

Beilstein J. Org. Chem. 2021, 17, 1641–1688, doi:10.3762/bjoc.17.116

• modifications in the middle [70] resembled the P-form helices formed by PNA–PNA and PNA–DNA–PNA more than the PNA–DNA structure [39]. Ly and co-workers synthesized α-modified PNAs derived from ʟ-arginine (α-GPNA, Figure 5) and showed that the positively charged guanidinium group increased the stability of PNA

• duplexes with complementary DNA and RNA, without compromising the sequence selectivity, and improved the cellular uptake of PNA [71]. The same group later demonstrated that GPNA derived from ᴅ-arginine formed more stable duplexes with RNA and was readily taken up by both human somatic and embryonic stem

• cells [72]. GPNA targeting the transcriptional start-site of the human E-cadherin gene had potent and sequence-specific antisense activity and was less toxic to the cells than the PNA–polyarginine conjugate [73]. Interestingly, the α-arginine modification in either ʟ- or ᴅ-configuration destabilized PNA

Beyond ribose and phosphate: Selected nucleic acid modifications for structure–function investigations and therapeutic applications

• Christopher Liczner,
• Kieran Duke,
• Gabrielle Juneau,
• Martin Egli and
• Christopher J. Wilds

Beilstein J. Org. Chem. 2021, 17, 908–931, doi:10.3762/bjoc.17.76

• in the vicinity of a hydrophobic patch that is surrounded by lysine and arginine residues [15]. The latter generate an electric field that could polarize sulfur atoms (the PS2 group still carries a negative charge), thereby enhancing the interaction of the PS2 moiety with the edge of phenylalanine as

Enhanced target cell specificity and uptake of lipid nanoparticles using RNA aptamers and peptides

• Roslyn M. Ray,
• Anders Højgaard Hansen,
• Maria Taskova,
• Bernhard Jandl,
• Jonas Hansen,
• Citra Soemardy,
• Kevin V. Morris and
• Kira Astakhova

Beilstein J. Org. Chem. 2021, 17, 891–907, doi:10.3762/bjoc.17.75

• charged peptide Tat has previously been demonstrated to be effective as an excipient species to increase the uptake through the negatively charged BBB [9][18]. Tat (sequence: H-YGRKKRRQRRR-NH2) is an arginine-rich short cell-penetrating peptide derived from the natural nuclear Tat protein of HIV-1 [19][20

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

Semiautomated glycoproteomics data analysis workflow for maximized glycopeptide identification and reliable quantification

• Steffen Lippold,
• Arnoud H. de Ru,
• Jan Nouta,
• Peter A. van Veelen,
• Magnus Palmblad,
• Manfred Wuhrer and
• Noortje de Haan

Beilstein J. Org. Chem. 2020, 16, 3038–3051, doi:10.3762/bjoc.16.253

• database including 71,591 protein sequences (20,205 from Swiss-Prot and 51,386 from TrEMBL). The C-terminal cleavage of lysine and arginine and a maximum of two missed cleavages was allowed. A tolerance of 10 ppm was applied for the precursors and 20 ppm for fragment ions. A carbamidomethylation was set as

Selected peptide-based fluorescent probes for biological applications

• Debabrata Maity

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

• membrane-bound receptors interact strongly with short peptidic segments of a larger protein chain, for example, recognition of the RGD sequence (arginine–glycine–aspartic acid; Arg–Gly–Asp) by integrin receptors. They use noncovalent interactions including salt bridges [5]. Vancomycin, a glycopeptide

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

• mostly on ligands that recognize either positively or negatively charged patches on a protein surface, discussing the molecules shown in Figure 1 in greater detail. Ligands designed to recognize positively charged regions, containing lysine (Lys) and arginine (Arg) residues, on a protein include

• 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

• arginine residues for this purpose. In this review, we focus on the use of protein-based NMR techniques to identify the binding sites of supramolecular ligands, particularly those recognizing charged patches, on protein surfaces. Table 1 presents a summary of the discussed NMR studies. We begin with a look

pH- and concentration-dependent supramolecular self-assembly of a naturally occurring octapeptide

• Goutam Ghosh and
• Gustavo Fernández

Beilstein J. Org. Chem. 2020, 16, 2017–2025, doi:10.3762/bjoc.16.168

• in mind, we synthesized an octapeptide, PEP-1, which contains two valine (Val) units and one leucine (Leu) unit as the hydrophobic residues and one glutamic acid (Glu) residue, two arginine (Arg) units, and one cysteine (Cys) substituent as polar moieties (Scheme 1). This choice of amino acids

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

• challenge is most pronounced with large substrates, such as proteins, oligonucleotides, or nanoparticles, due to the permeability barriers formed by the lipophilic core of the cell membrane [18][19]. In recent decades, the use of arginine-rich cell-penetrating peptides (CPPs) as carriers has emerged as an

• )pyrrole (GCP) cation 1 as a synthetic analogue of the guanidinium cations, somehow a “super-guanidinium” conceived to drive “arginine magic” [20][21] to the extreme (Figure 1) [23]. The power of the Schmuck cation to bind carboxylate and phosphate anions in competitive water has several origins [22

• results further support the importance of GAG binding to the uptake of Schmuck cations. Arginine-rich CPPs are of general interest in gene delivery. However, a long linear CPP sequence with at least eight to nine arginine residues is necessary. In comparison to arginine-rich CPPs, Schmuck peptides form

Synthesis, docking study and biological evaluation of ᴅ-fructofuranosyl and ᴅ-tagatofuranosyl sulfones as potential inhibitors of the mycobacterial galactan synthesis targeting the galactofuranosyltransferase GlfT2

• Marek Baráth,
• Jana Jakubčinová,
• Zuzana Konyariková,
• Stanislav Kozmon,
• Katarína Mikušová and
• Maroš Bella

Beilstein J. Org. Chem. 2020, 16, 1853–1862, doi:10.3762/bjoc.16.152

• will be discussed below. The observed binding modes of the docked molecules revealed some common interaction patterns. Interactions of the PO4 group with a metal ion and arginine R171 were observed in almost all docking poses and in some cases the C2 hydroxy group also interacted with a metal ion. The

• hydroxy group and the phenyl ring created a cation–π stacking interaction with the arginine R171 side chain (Figure 2). The observed theoretical binding energy in kcal/mol represented by the docking scores and the predicted binding affinities for the UDP-Galf, fructofuranose, and tagatofuranose compounds

Facile synthesis of 7-alkyl-1,2,3,4-tetrahydro-1,8-naphthyridines as arginine mimetics using a Horner–Wadsworth–Emmons-based approach

• Rhys A. Lippa,
• John A. Murphy and
• Tim N. Barrett

Beilstein J. Org. Chem. 2020, 16, 1617–1626, doi:10.3762/bjoc.16.134

• cores for these compounds in high yields (63–83% over 3 steps) with no need for chromatography. Key to this transformation is the phosphoramidate protecting group, which is stable to metalation steps. Keywords: arginine; Horner–Wadsworth–Emmons; integrin; phosphoramidate; tetrahydronaphthyridine

• ; Introduction Tetrahydronaphthyridines are prominent in peptidomimetic pharmaceuticals as arginine mimetics and they are widely used in Arg–Gly–Asp (RGD) peptide mimetics such as αv integrin inhibitors [1]. Tetrahydronaphthyridines represent less basic but more permeable alternatives to arginine (pKa ≈ 7 versus

• 13.8) [1] replicating the side-on salt-bridge binding interaction made between the guanidinium functionality of arginine and an aspartic acid residue in the protein. Consequently, this moiety has been used in various integrin inhibitors (Figure 1) [2][3][4][5][6][7][8]. Current routes to install

A systematic review on silica-, carbon-, and magnetic materials-supported copper species as efficient heterogeneous nanocatalysts in “click” reactions

• Pezhman Shiri and
• Jasem Aboonajmi

Beilstein J. Org. Chem. 2020, 16, 551–586, doi:10.3762/bjoc.16.52

Synthesis of 4-amino-5-fluoropyrimidines and 5-amino-4-fluoropyrazoles from a β-fluoroenolate salt

• Tobias Lucas,
• Jule-Philipp Dietz and
• Till Opatz

Beilstein J. Org. Chem. 2020, 16, 445–450, doi:10.3762/bjoc.16.41

• arginine, where the desired pyrimidine 10q was also only observed in trace amounts while the majority of the starting material remained unchanged. Synthesis of fluorinated aminopyrazoles As in the cyclocondensation with amidines, the reaction of 8 with other bifunctional nucleophiles could also result in

Current understanding and biotechnological application of the bacterial diterpene synthase CotB2

• Ronja Driller,
• Daniel Garbe,
• Norbert Mehlmer,
• Monika Fuchs,
• Keren Raz,
• Dan Thomas Major,
• Thomas Brück and
• Bernhard Loll

Beilstein J. Org. Chem. 2019, 15, 2355–2368, doi:10.3762/bjoc.15.228

• involved in coordination of water molecules in the water network around the catalytic Mg2+ ions. The pyrophosphate sensor motif In a recent review, the presence of a “pyrophosphate sensor”, an arginine 46 amino acid residues upstream of the NSE motif, was discussed as a universal feature of bacterial TPSs

Complexation of chiral amines by resorcin[4]arene sulfonic acids in polar media – circular dichroism and diffusion studies of chirality transfer and solvent dependence

• Bartosz Setner and
• Agnieszka Szumna

Beilstein J. Org. Chem. 2019, 15, 1913–1924, doi:10.3762/bjoc.15.187

• ), H-Val-OMe (∙HCl). After a few minutes, complexes of 1 with lysine, arginine and histidine methyl esters precipitated. The obtained solids were isolated and dried in vacuum. 1(LysOMe)2, yield 71% (10 mg). 1H NMR (600 MHz, methanol-d4, δ) 7.28 (s, 4H), 4.58 (t, J = 7.9 Hz, 4H), 4.26 (dd, J = 14.0 Hz

Synthesis of (macro)heterocycles by consecutive/repetitive isocyanide-based multicomponent reactions

• Angélica de Fátima S. Barreto and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2019, 15, 906–930, doi:10.3762/bjoc.15.88

• reactions in the synthesis of macrocycles (which were considered as macroheterocycles in the context of this review). In this respect, Wessjohann et al. developed a methodology for the synthesis of cyclic RGD pentapeptoids (RGD = arginine-glycine-aspartic acid) by consecutive Ugi reactions [32]. This was

N-Acylated amino acid methyl esters from marine Roseobacter group bacteria

• Hilke Bruns,
• Lisa Ziesche,
• Nargis Khakin Taniwal,
• Laura Wolter,
• Thorsten Brinkhoff,
• Jennifer Herrmann,
• Rolf Müller and
• Stefan Schulz

Beilstein J. Org. Chem. 2018, 14, 2964–2973, doi:10.3762/bjoc.14.276

• , tryptophan, arginine, or phenylalanine [30][31][32]. They all carry long chain saturated or unsaturated acyl chains similar to those reported here. Recently, derivatives of the hydrophobic amino acids valine, leucine and isoleucine were also reported [33]. These compounds are produced by a family of acyl