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

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

• higher yield of validamycin A (25) from Streptomyces hygroscopicus 5008 together with more rapid protein synthesis and sugar consumption by subjecting cultures to one or more NaOH shocks [66]. Ren et al. obtained enhanced ε-poly-ʟ-lysine (ε-PL, 26) production by acidic pH shock of Streptomyces sp. M-Z18

Palladium-catalyzed three-component radical-polar crossover carboamination of 1,3-dienes or allenes with diazo esters and amines

• Geng-Xin Liu,
• Xiao-Ting Jie,
• Ge-Jun Niu,
• Li-Sheng Yang,
• Xing-Lin Li,
• Jian Luo and
• Wen-Hao Hu

Beilstein J. Org. Chem. 2024, 20, 661–671, doi:10.3762/bjoc.20.59

• owing to their wide applications in medicinal chemistry [1][2][3][4][5]. γ- and ε-AA derivatives are widely distributed in peptide natural products, bioactive molecules, and drugs, such as pregabalin, baclofen, ε-aminocaproic acid and lysine (Scheme 1a) [6][7][8][9][10][11][12]. The number of reported

Possible bi-stable structures of pyrenebutanoic acid-linked protein molecules adsorbed on graphene: theoretical study

• Yasuhiro Oishi,
• Motoharu Kitatani and
• Koichi Kusakabe

Beilstein J. Org. Chem. 2024, 20, 570–577, doi:10.3762/bjoc.20.49

• , respectively. The solid, broken, and dotted red lines represent the rotation axis. Atomic geometry is visualized by Xcrysden [10] throughout this paper. (b) Schematic diagram of the dehydration-condensation structure of a hypothetical protein and PASE. Lys indicates lysine, and RC is the active center of the

Radical chemistry in polymer science: an overview and recent advances

• Zixiao Wang,
• Feichen Cui,
• Yang Sui and
• Jiajun Yan

Beilstein J. Org. Chem. 2023, 19, 1580–1603, doi:10.3762/bjoc.19.116

• amino acid sequence of mfp-1, mfp-3, and mfp-5 (Y: DOPA, K: lysine). B) Scheme showing examples of the adhesive and cohesive properties of catechol-containing proteins. R represents the remainder of the mfp’s. Scheme 3 redrawn from [10]. Activation–deactivation equilibrium in nitroxide-mediated

Computational model predicts protein binding sites of a luminescent ligand equipped with guanidiniocarbonyl-pyrrole groups

• Neda Rafieiolhosseini,
• Matthias Killa,
• Thorben Neumann,
• Niklas Tötsch,
• Jean-Noël Grad,
• Alexander Höing,
• Thies Dirksmeyer,
• Jochen Niemeyer,
• Christian Ottmann,
• Shirley K. Knauer,
• Michael Giese,
• Jens Voskuhl and
• Daniel Hoffmann

Beilstein J. Org. Chem. 2022, 18, 1322–1331, doi:10.3762/bjoc.18.137

• , the GCP and lysine beads are found near the hydroxyl groups of the aspartic acid residues of the protein. The second energy minimum of the ligand is related to the first one by the C2 symmetry of 14-3-3ζ. In contrast, in the presence of C-Raf peptides the minimum energy positions of 1 move to the

• center of the ω where the AIE moieties hover above the central pore (Figure 6c and d). In these two conformations, at least one of the lysine groups lies at the minimum energy position of the lysine affinity map (more information about the affinity map is given in the “Energy grids” section). Both GCP

• of 14-3-3ζ with GCP and lysine ligands, we proceeded as follows. The GCP and lysine ligand geometries were calculated in OpenBabel v2.3.2 [30] starting from a SMILES string of each ligand. The van der Waals radii of ligand atoms were added automatically by OpenBabel. The 14-3-3ζ structure (PDB 4IHL

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

Amamistatins isolated from Nocardia altamirensis

• Till Steinmetz,
• Wolf Hiller and
• Markus Nett

Beilstein J. Org. Chem. 2022, 18, 360–367, doi:10.3762/bjoc.18.40

• in the HMBC spectrum unveiled the ester linkage with a lysine residue. The spin system of the latter includes proton resonances at δH 4.62 (dd, J = 9.9, 5.3 Hz, H-20), 2.03 ppm (m, H-21a), 1.90 ppm (m, H-21b), 1.58 (m, H-22a), 1.49 (m, H-22b), 1.76 (m, H-23a), 1.60 (m, H-23b), and 3.22 ppm (m, H2-24

• formula of C35H53N5O8 was determined by HRESIMS with a molecular ion at m/z 672.3966 [M + H]+ (calcd for C35H54N5O9, 672.3972). Similar to 3, compound 4 is also missing a formyl group at the ε-amino group of its lysine residue. However, its increased mass of 16 Da indicates the presence of an additional

• next to the ε-amino group in the lysine moiety. The assumption of a hydroxylamine function is consistent with tandem MS data, which showed mass shifts of 16 Da in the corresponding region in comparison to compound 3. Compound 5 (0.7 mg) was obtained as a clear oil. Its molecular formula of C36H53N5O10

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

• -Lysine binding [39]. Although PLP is not a reported neuraminidase inhibitor, its main interaction in the active site could be reasoned based on previous results with sialic acid-derived phosphonate analogues. In this regard, it has been suggested that the inhibition of different strains of influenza

Synthesis and late stage modifications of Cyl derivatives

• Phil Servatius and
• Uli Kazmaier

Beilstein J. Org. Chem. 2022, 18, 174–181, doi:10.3762/bjoc.18.19

• B (Figure 1) is a cyclic tetrapeptide with a rather unusual epoxyketone side chain and was found to be a strong inhibitor of histone deacetylases (HDACs) [4][5]. HDACs are nuclear isozymes that regulate gene transcription via a dynamic process of acetylation and deacetylation of lysine residues of

• ]. Three of these enzyme classes (I, II, and IV) contain Zn2+ within the active site, and therefore these enzymes can be affected by typical Zn2+-binding HDAC inhibitors. In cellular systems, an acetylated lysine of a histone is entering the cavity of the active site and gets coordinated to Zn2

• +. Subsequent attack of water forms a tetrahedral intermediate which results in a cleavage of the acetylated lysine. Most HDAC inhibitors act as substrate mimics and contain a zinc-binding motif. They competitively interact with the HDACs to form stable intermediates and therewith block the active site. Many

Peptide stapling by late-stage Suzuki–Miyaura cross-coupling

• Hendrik Gruß,
• Rebecca C. Feiner,
• Ridhiwan Mseya,
• David C. Schröder,
• Michał Jewgiński,
• Kristian M. Müller,
• Rafał Latajka,
• Antoine Marion and
• Norbert Sewald

Beilstein J. Org. Chem. 2022, 18, 1–12, doi:10.3762/bjoc.18.1

• of biomolecules [35][36][37]. The approaches by Buchwald and Pentelute are suitable for selective, bioorthogonal labelling of cysteine- [38][39][40] and lysine-containing [41][42] peptides and proteins using stochiometric amounts of pre-formed Pd(II)-aryl complexes. They can further be applied for

• -diaminobutyric acid (Dab), ornithine (Orn), or lysine (Lys). Utilising the Alloc protecting group allowed the coupling of 4-carboxyphenylboronic acid once the linear sequence had been synthesised (Scheme 2C). The intramolecular SMC between 6- or 7-bromotryptophan and the boronic acid afforded the stapled

• in i + 4-position of the linear axin CBD sequence aAxWt were substituted by tryptophan and lysine, respectively, to have a higher analogy to the lysine modified SMC stapled peptides. Following the indications of DFT calculations, stapled peptide P5 was synthesised by modification of lysine in the i

Constrained thermoresponsive polymers – new insights into fundamentals and applications

• Patricia Flemming,
• Alexander S. Münch,
• Andreas Fery and
• Petra Uhlmann

Beilstein J. Org. Chem. 2021, 17, 2123–2163, doi:10.3762/bjoc.17.138

Cationic oligonucleotide derivatives and conjugates: A favorable approach for enhanced DNA and RNA targeting oligonucleotides

• Mathias B. Danielsen and
• Jesper Wengel

Beilstein J. Org. Chem. 2021, 17, 1828–1848, doi:10.3762/bjoc.17.125

• resistance was maintained [75]. The attachment of a lysine onto the aminohexyl residue resulted in a lysylaminohexyl group (monomer 40) which displayed a gradual increase in Tm upon incorporation of up to three modifications, and also improved the resistance against nuclease degradation relative to the

• relative to the downregulation of the reference ASO (Oblimersen) [91]. In an entirely different approach, the 2’-amino group of amino-LNA-thymine (amino-LNA-T) has been explored as an attachment point for various cationic groups. As one example, amino acids such as glycine, lysine, and proline in different

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

• vulnerabilities. Limited water solubility, especially for purine rich sequences, was noted in early studies. To improve water solubility and decrease aggregation, typical PNA designs place a lysine at the C-terminus (Figure 1) introducing a second positive charge in addition to the charge at the N-terminus of PNA

• [1]. Even with the additional lysine, the solubility of PNA decreases as the polymer length increases. PNA solubility in the HEPES buffer at pH 7.3 and 37 °C is estimated to be in the 0.1–0.5 mM range [12][13]. The hydrophobic nature and lack of electrostatic repulsion of the PNA backbone favors

• transitions between different binding modes of γ-hydroxymethyl-modified triplex-forming PNAs have been also explored [78]. Englund and Appella showed that PNA containing γ-modifications derived from ʟ-lysine formed stronger duplexes with DNA and RNA, while γ-modifications derived from ᴅ-lysine decreased the

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

Synthesis and physicochemical evaluation of fluorinated lipopeptide precursors of ligands for microbubble targeting

• Masayori Hagimori,
• Estefanía E. Mendoza-Ortega and
• Marie Pierre Krafft

Beilstein J. Org. Chem. 2021, 17, 511–518, doi:10.3762/bjoc.17.45

• hydrophobic chains (CnF2n+1, n = 6, 7, 8, 1–3) grafted through a lysine moiety on a hydrophilic chain composed of a lysine–serine–serine (KSS) sequence followed by 5 SG sequences. These F-lipopeptides are precursors of targeting lipopeptide conjugates. A hydrocarbon counterpart with a C10H21 chain (4) was

• (SG)5KSS peptide chain is assembled stepwise using a Fmoc solid-phase peptide synthesis procedure. In a second step, the two perfluoroalkylated chains are grafted to the peptide chain through a lysine moiety. Next, the surface activity of the synthesized lipopeptides is investigated by assessing their

• develop between the F-lipopeptide and perfluorohexane in the bubble’s interfacial film. Conclusion A series of lipopeptides carrying CnF2n+1 chains (n = 6, 7, 8, 1–3) or C10H21 chains (4) grafted through a lysine moiety on a peptide chain composed of a KSS sequence followed by 5 SG sequences were

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

• lysine residues. This approach is attractive as it can be directly applied to isotopically enrich unlabelled proteins, which may have been obtained previously from natural sources or as recombinant proteins under less demanding cell growth conditions. As shown in Figure 3, these fluorine tags consist, in

• combined with the aforementioned chemical approaches based on cysteine and lysine modification. It is worth noting that for small proteins and peptides the chemical incorporation of the desired fluorinated amino acids using SPPS protocols still remains the method of choice, as it enables the site-specific

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

• peptidic arms equipped with lysine and an artificial strong anion binding site, the guanidinocarbonylpyrrole (GCP) moiety (Figure 2A). These arms also contain tryptophan for dissimilar aromatic interactions with different nucleobases. The fluorescence intensity of probe 1 increases by more than 4-fold at

• fluorescent probes for nucleic acids detection. The first probe 2 is a pyrene-based peptide beacon containing two Trp–Thr–Lys tripeptide arms attached to a central lysine spacer (Figure 3A) [34]. Unbound peptide beacon 2 in folded form exhibits typical pyrene excimer emission at 490 nm. Peptide beacon 2

• interacts effectively with double-stranded DNA (dsDNA) as positively charged lysine residues are expected to interact with the phosphate backbone electrostatically. Upon binding to dsDNA, it undergoes a conformational change from the folded to an extended form that switches the fluorescence signal from

Encrypting messages with artificial bacterial receptors

• Pragati Kishore Prasad,
• Naama Lahav-Mankovski,
• Leila Motiei and
• David Margulies

Beilstein J. Org. Chem. 2020, 16, 2749–2756, doi:10.3762/bjoc.16.225

• grow in the same medium on a shaking incubator at 30 °C. Fluorescent imaging to study labeling during bacterial growth. The bacterial sample to be imaged was normalized to an OD600 = 0.3, suspended in 100 µL PBS, and placed on a glass-bottom dish (P35G-1.5-14-C; MatTek) precoated with poly-ʟ-lysine

Enzyme-instructed morphological transition of the supramolecular assemblies of branched peptides

• Dongsik Yang,
• Hongjian He and
• Bing Xu

Beilstein J. Org. Chem. 2020, 16, 2709–2718, doi:10.3762/bjoc.16.221

• assemblies of the peptides. The attachment of DEDDDLLI sequences to the ε-amine of the lysine residue of a tetrapeptide produces branched peptides that form micelles. Upon the proteolytic cleavage of the branch, catalyzed by proteinase K, the micelles turn into nanofibers. We also found that the acetylation

• peptides has received limited attention [2][32][33][34][35][36][37]. For example, Stupp et al. reported that a cell adhesion epitope, RGDS, acts as a branch to peptide amphiphiles for making hydrogels via self-assembly [34][36]. Ulijn et al. connected Fmoc-DAARRGG to a lysine side chain for incorporation

• assemblies of the peptides. The conjugation of Asp–Glu–Asp–Asp–Asp–Leu–Leu–Ile–Gly (DEDDDLLIG) sequences to the ε-amine of the lysine residue of a tetrapeptide Nap–ᴅ-Phe–ᴅ-Phe–ᴅ-Lys–ᴅ-Tyr (Nap-ffky) [9] produces the branched peptide 1, which forms micelles (Figure 1). When proteinase K catalyzed the

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

• phosphonate groups. While sulfonato-calix[4]arenes can bind unmodified Lys and Arg residues, their strength lies in the recognition and even tighter binding of methylated lysines [29]. Their binding affinity increases 70-fold from unmethylated over mono- and di- to trimethylated lysine, as every methyl group

• adds more hydrophobic interactions with the aromatic side walls of the bowl-shaped calixarene core. A similar, but even more pronounced trend, is observed for the pumpkin-shaped macrocycle cucurbit[7]uril, favoring the trimethylated over unmethylated lysine by a factor of 3500 [49]. Methylated lysines

Naphthalene diimide–amino acid conjugates as novel fluorimetric and CD probes for differentiation between ds-DNA and ds-RNA

• Annike Weißenstein,
• Myroslav O. Vysotsky,
• Ivo Piantanida and
• Frank Würthner

Beilstein J. Org. Chem. 2020, 16, 2032–2045, doi:10.3762/bjoc.16.170

• [nm] = 581; Φfl = 0.21. Synthesis of (S)-N,N'-bis((3-(trimethylammonium)propyl)amino)-2- (5-amino-5-carboxypentyl)amino-6-chloro-1,4,5,8-naphthalenetetracarboxylic acid diimide dichloride (3b): Diimide (1, 100 mg, 190 µmol) and Nα-(tert-butoxycarbonyl)-ʟ-lysine (95.0 mg, 390 µmol) were placed under

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

• far exceeds the related tetrapeptide analogues with arginine or lysine residues. As a result, the gene transfection efficiency of 13 is better than that of polyethylenimine (PEI) with a large number of charges, which is one of the current standards in gene transfection. The uptake takes place through

• offsetting a charge repulsion of the extra lysine residues, and thus allowing the formation of stable cationic nanofibers. These nanoaggregates, assembled from the monomer 16, are efficient gene transfection vectors. However, the control peptide 17, which cannot self-assemble into nanotubes, shows negative