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

• developed to facilitate and improve both the identification and quantification of glycopeptides. Here, a selection of these tools was combined and evaluated with the aim of establishing a robust glycopeptide detection and quantification workflow targeting enriched glycoproteins. For this purpose, a tryptic

• ]. Advances in MS technologies tremendously enhanced the detection and informative fragmentation of glycopeptides in the past years [9]. The large amount of highly complex data acquired using these technologies shifted the major bottleneck in glycopeptide analysis to the data processing steps. Next to the

• coverage was maximized by combining all measurements. For the MS1-based assignment, the variation between replicates was found in the minor glycan species, which were on the borderline of the limit of detection. Further, the stochastic nature of MS/MS selection is a known factor, which may cause

Secondary metabolites of Bacillus subtilis impact the assembly of soil-derived semisynthetic bacterial communities

• Heiko T. Kiesewalter,
• Carlos N. Lozano-Andrade,
• Mikael L. Strube and
• Ákos T. Kovács

Beilstein J. Org. Chem. 2020, 16, 2983–2998, doi:10.3762/bjoc.16.248

• , and Paenibacillus. The remaining most abundant genera in the mock communities were below the detection limit. The comparison of the abundance ratios between the control communities and B. subtilis WT-treated communities revealed that Lysinibacillus and Viridibacillus were significantly decreased 9.4

• indicated a significantly lower (P ≤ 0.01) abundance (0.03%) compared to the control communities. Notably, in two of the WT-treated community replicates, Viridibacillus was below the detection level. Nevertheless, the abundance of this genus in the sfp-treated communities (0.26%) was statistically not

• back to different growth rates among the present species. A substantial shift in the community compositions was observed between in vivo and in vitro communities since the majority of the genera present in the in vitro communities was below the detection limit in the soil sample. However, during the 12

Selected peptide-based fluorescent probes for biological applications

• Debabrata Maity

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

• labeled with environmentally sensitive/FRET fluorophores have allowed direct detection/monitoring of biomolecules in aqueous media and in live cells. In this review, key peptide-based approaches for different biological applications are presented. Keywords: fluorescent probe; fluorophores; molecular

• for biomolecule detection [27][28]. Being intrinsically modular, peptide scaffolds also allow the attachment of multiple fluorophores simultaneously [29]. It provides the opportunity of developing ratiometric fluorescent sensors from the interaction between multiple fluorophores (Figure 1B

• to perform FRET in vitro and in vivo, particularly in living cells [30]. FRET-based peptide probes are heavily used for ratiometric fluorescence detection of biomolecules. Pyrene-functionalized oligonucleotides and locked nucleic acids (LNAs) are considerably used for targeting nucleic acids [31

Controlled decomposition of SF₆ by electrochemical reduction

• Sébastien Bouvet,
• Bruce Pégot,
• Stéphane Sengmany,
• Erwan Le Gall,
• Eric Léonel,
• Anne-Marie Goncalves and
• Emmanuel Magnier

Beilstein J. Org. Chem. 2020, 16, 2948–2953, doi:10.3762/bjoc.16.244

• , CNRS, ICMPE, UMR 7182, 2 rue Henri Dunant, 94320 Thiais, France 10.3762/bjoc.16.244 Abstract The electroreduction of SF6 is shown at ambient temperature in acetonitrile using an array of platinum microelectrodes to improve the electrical detection. Its half reduction potential occurs at −2.17 V vs Fc

• . All potentials were measured against a pseudo silver reference electrode (SRE). The addition of ferrocene in the electrolyte gives access to an internal reference [33]. In order to improve the current detection level of SF6, platinum disk electrodes were used as working electrode (Pt

• counter electrode. Electrochemical measurements were covered by a wide range of a potentiostat for more effective current detection. A potentiostat–galvanostat such as Princeton Applied Research Model 263 was monitored by its front panel and analogue-to-digital conversion was provided by «Powerlab». A

Using multiple self-sorting for switching functions in discrete multicomponent systems

• Amit Ghosh and
• Michael Schmittel

Beilstein J. Org. Chem. 2020, 16, 2831–2853, doi:10.3762/bjoc.16.233

• reversibility was achieved by the addition of the rhodium porphyrin 19 that reversed the system reviving the state SelfSORT-I. Since both self-sorted states exhibited a distinct fluorescence due to the changes at the zinc porphyrin sites, luminescence was used for the selective detection of DABCO in a mixture

3-Acetoxy-fatty acid isoprenyl esters from androconia of the ithomiine butterfly Ithomia salapia

• Florian Mann,
• Daiane Szczerbowski,
• Lisa de Silva,
• Melanie McClure,
• Marianne Elias and
• Stefan Schulz

Beilstein J. Org. Chem. 2020, 16, 2776–2787, doi:10.3762/bjoc.16.228

• vicinity of the male wings, although the evaporation rate might be increased by erection of the androconia hairpencils (Figure 1). Alternatively, direct or close contact might be needed for detection, probably taking place during contact of the female antennae with the male wings. What this potential

Selective recognition of ATP by multivalent nano-assemblies of bisimidazolium amphiphiles through “turn-on” fluorescence response

• Rakesh Biswas,
• Surya Ghosh,
• Shubhra Kanti Bhaumik and
• Supratim Banerjee

Beilstein J. Org. Chem. 2020, 16, 2728–2738, doi:10.3762/bjoc.16.223

• presence of positive surface charges on the multivalent aggregates led to ATP binding which was accompanied by a significant increase in the excimeric emission intensity. This provided a convenient way of monitoring ATP binding in a “turn-on” mode and an efficient detection of ATP was achieved in aqueous

• buffer and also in buffer containing 150 mM NaCl at physiological pH value. Furthermore, the multivalent aggregates demonstrated a significant selectivity in ATP detection over ADP, AMP and pyrophosphate. Keywords: amphiphile; ATP; excimer; multivalency; self-assembly; Introduction Supramolecular anion

• years, anion responsive materials [5][6] have also emerged as an interesting class of stimuli-responsive materials. Among the different varieties of anionic species, the selective and sensitive detection of bio-anions is particularly important due to their involvement in various biological functions

Nocarimidazoles C and D, antimicrobial alkanoylimidazoles from a coral-derived actinomycete Kocuria sp.: application of ¹J_C,H coupling constants for the unequivocal determination of substituted imidazoles and stereochemical diversity of anteisoalkyl chains in microbial metabolites

• Md. Rokon Ul Karim,
• Enjuro Harunari,
• Amit Raj Sharma,
• Naoya Oku,
• Kazuaki Akasaka,
• Daisuke Urabe,
• Mada Triandala Sibero and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2020, 16, 2719–2727, doi:10.3762/bjoc.16.222

• purification was achieved by preparative HPLC (Cosmosil AR-II, Nacalai Tesque Inc., 10 × 250 mm, 4 mL/min, UV detection at 254 nm) with an isocratic elution of MeCN/0.1% HCO2H (42:58) to afford nocarimidazole C (1, 2.4 mg, tR 8.45 min), nocarimidazole D (2, 3.2 mg, tR 14.9 min), nocarimidazole A (3, 3.8 mg, tR

Optical detection of di- and triphosphate anions with mixed monolayer-protected gold nanoparticles containing zinc(II)–dipicolylamine complexes

• Lena Reinke,
• Julia Bartl,
• Marcus Koch and
• Stefan Kubik

Beilstein J. Org. Chem. 2020, 16, 2687–2700, doi:10.3762/bjoc.16.219

• /bjoc.16.219 Abstract Gold nanoparticles covered with a mixture of ligands of which one type contains solubilizing triethylene glycol residues and the other peripheral zinc(II)–dipicolylamine (DPA) complexes allowed the optical detection of hydrogenphosphate, diphosphate, and triphosphate anions in

• )–dipicolylamine complexes beyond 25% had a negative impact on the limit of detection and the optical response. Transmission electron microscopy provided evidence that the changes of the nanoparticle properties observed in the presence of the phosphates were due to a nanoparticle crosslinking, consistent with the

• conformational reorganization of the linker connecting the chromophore with the surface. The likely most frequently used strategy of analyte detection relies on the color change of AuNP solutions resulting from analyte-induced nanoparticle crosslinking. Depending on whether soluble or insoluble aggregates are

Leveraging glycomics data in glycoprotein 3D structure validation with Privateer

• Haroldas Bagdonas,
• Daniel Ungar and
• Jon Agirre

Beilstein J. Org. Chem. 2020, 16, 2523–2533, doi:10.3762/bjoc.16.204

• formed to another carbohydrate unit. Crucially, the linkage detection in Privateer does not rely at all on metadata present in the structure file. Instead, linkages are identified based on the perceived chemistry of the input model: which atoms are close enough – but not too close – to be plausibly

• , glycoprotein models deposited in the PDB feature flaws ranging from minor irregularities to gross modelling errors [14][17][41][64]. The automated validation of minor irregularities was already possible with automated tools such as pdb-care [37], CARP [65], and Privateer [24]. However, the automated detection

• of gross modelling errors is currently a challenge due to the lack of publicly available tools. Our newly developed computational bridge between structural biology and glycomics databases makes the detection of gross modelling errors easier, as demonstrated by the following examples. Example 1 – 2H6O

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

• . If a signal broadens beyond detection and thus disappears from the spectrum, be it due to aggregation or intermediate exchange kinetics, it is also impossible to trace its trajectory and determine the chemical shift perturbation. In the case of a bifunctional GCP ligand binding to survivin [46], the

Computational tools for drawing, building and displaying carbohydrates: a visual guide

• Kanhaya Lal,
• Rafael Bermeo and
• Serge Perez

Beilstein J. Org. Chem. 2020, 16, 2448–2468, doi:10.3762/bjoc.16.199

• information, coupled with the emergence of new platforms and technologies, has benefitted glycoscience to the point of enabling the detection and high-resolution determination and representation of complex glycans [1]. Increasing numbers of carbohydrate sequences have accumulated throughout extensive work in

Styryl-based new organic chromophores bearing free amino and azomethine groups: synthesis, photophysical, NLO, and thermal properties

• Anka Utama Putra,
• Deniz Çakmaz,
• Nurgül Seferoğlu,
• Alberto Barsella and
• Zeynel Seferoğlu

Beilstein J. Org. Chem. 2020, 16, 2282–2296, doi:10.3762/bjoc.16.189

• excitation leads to a red-shifted emission which is viable for the detection of various substrates in biological tissues and samples [28][29][30]. Recently, there was an increasingly growing interest in studies regarding push-pull organic molecules comprising of the dicyanomethylene group as a strong

• light indicated that the dye was deprotonated. Indeed, the addition of only 5 equiv of TFA regenerated the light yellow color of the solution indicative for the reversed protonation of 12. All dyes, except 8, showed this reversibility. Furthermore, the limits of detection (LOD) and quantification (LOQ

Tools for generating and analyzing glycan microarray data

• Akul Y. Mehta,
• Jamie Heimburg-Molinaro and
• Richard D. Cummings

Beilstein J. Org. Chem. 2020, 16, 2260–2271, doi:10.3762/bjoc.16.187

• utilizes a different mechanism of binding the ligands to the surface. Choosing an appropriate surface often depends on the type of glycoconjugates to be printed, as well as the GBP and detection wavelengths used. For example, a nitrocellulose surface has an intrinsic high background when scanned at 488 nm

• wavelength, thus making the surface incompatible with detection reagents which rely on this wavelength. While it is possible to use nitrocellulose slides at 488 nm wavelength with lower detector sensitivity (PMT setting) and lower scan power (laser power), it might be more advisable to check other

• placed on slide (≈70 μL), and a coverslip is placed on top to spread the sample evenly across the array surface of the slide and helps to prevent evaporation during the assay. Detailed protocols for either method of microarray experiment and that cover different types of samples and detection methods are

GlypNirO: An automated workflow for quantitative N- and O-linked glycoproteomic data analysis

• Toan K. Phung,
• Cassandra L. Pegg and
• Benjamin L. Schulz

Beilstein J. Org. Chem. 2020, 16, 2127–2135, doi:10.3762/bjoc.16.180

• assumed to not quantitatively affect detection. These results were concatenated into the final output file, where columns are the different samples and rows are the different peptide and glycoforms that have been analysed. The protein name of each glycosylated protein detected in the analysis was also

Clustering and curation of electropherograms: an efficient method for analyzing large cohorts of capillary electrophoresis glycomic profiles for bioprocessing operations

• Ian Walsh,
• Matthew S. F. Choo,
• Sim Lyn Chiin,
• Amelia Mak,
• Shi Jie Tay,
• Pauline M. Rudd,
• Yang Yuansheng,
• Andre Choo,
• Ho Ying Swan and
• Terry Nguyen-Khuong

Beilstein J. Org. Chem. 2020, 16, 2087–2099, doi:10.3762/bjoc.16.176

• to facilitate better peak picking and quantitation with electropherograms that were composed of heterogeneous peak shapes in our glycan analysis. Peak detection and quantitation of non-Gaussian peaks using Riemann approximation Quantitation of sets of electropherograms that were similar (i.e

• µm i.d. uncoated bare fused capillary, HR-NCHO separation gel buffer (Sciex). The applied electric field strength was 1500 V/cm with the cathode at the injection side and the anode at the detection side (reversed polarity). Samples were electrokinetically injected using 1kV for 5 s. For migration

Isolation and structure determination of a tetrameric sulfonyl dilithio methandiide in solution based on crystal structure analysis and ⁶Li/¹³C NMR spectroscopic data

• Jürgen Vollhardt,
• Hans Jörg Lindner and
• Hans-Joachim Gais

Beilstein J. Org. Chem. 2020, 16, 2057–2063, doi:10.3762/bjoc.16.172

• dynamics were poor solubility and problems to locate the 13C signals of the dianionic C atoms or the detection of only broad ones. Knowledge of the solution structure of dilithio methandiides would be, however, highly desirable in order to obtain a more complete understanding of the reactivity and

• coordination chemistry in general, and of the dianionic C atom in particular. During the structural investigation of 2a it was observed that the Li2O-free methandiide is in contrast to (2a)6·Li2O·(THF)6 readily soluble in THF. 6Li and 13C NMR spectroscopy of 2a had led to the detection of an aggregate, a

• Li2 (δ = 1.17 pm) [15][51][52][53]. Essential for the success of the NMR spectroscopic investigation of 2a was the 13C,6Li labelling of the dilithio methandiide. It allowed the detection of the otherwise low intensity signals of the dianionic carbon atoms of the aggregates and the attainment of

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

• sensitivity to particular target, read-out accuracy, limits of detection, and selectivity at biorelevant conditions. Experimental All solvents were purchased from commercial sources and used as received. Solvents for spectroscopic studies were of spectroscopic grade. Polynucleotides poly(dA-dT)2, poly(AU

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

• ), here exemplified by asparagusic acid. A persistent challenge in this evolution is the simultaneous and quantitative detection of cytosolic delivery and cytotoxicity in a high-throughput format. Here, we show that the combination of the HaloTag-based chloroalkane penetration assay (CAPA) with automated

• unorthodox COC chemistry covering ETPs [52], diselenolanes [53], and benzopolysulfanes [54], the activity gradually increased. The Achilles heel of much research on new transporters for cellular uptake, from CPPs and Schmuck cations to CPDs and COCs, is the quantitative detection of the delivery in the

• with the HC CAPA. To quantify the impact of the HC CAPA on the detection of the cytosolic delivery, the newly introduced peptide-based COC 23 was evaluated for the transport of a model protein with the new analytical improvements. With a CP50 value of 7.3 ± 0.5 μM with the mitochondrial mask, complex

Design, synthesis and application of carbazole macrocycles in anion sensors

• Alo Rüütel,
• Ville Yrjänä,
• Sandip A. Kadam,
• Indrek Saar,
• Mihkel Ilisson,
• Astrid Darnell,
• Kristjan Haav,
• Tõiv Haljasorg,
• Lauri Toom,
• Johan Bobacka and
• Ivo Leito

Beilstein J. Org. Chem. 2020, 16, 1901–1914, doi:10.3762/bjoc.16.157

• directed our efforts towards sensing carboxylates. The detection of these analytes is important in a number of areas and there is an obvious lack of easy-to-use sensing methods. Carboxylates are challenging analytes for two reasons. Firstly, binding is mainly achieved through either ion–ion interactions or

• transport phenomena and this semicircle was attributed to slow ion transfer kinetics at the ISM interfaces. Potentiometric calibrations in sodium acetate solutions were used to determine the linear ranges (R2 ≥ 0.999), slopes, and detection limits of the sensors (Table 2). Examples of the calibration curves

• variations in the position of the plug as a result of handling the reference electrode while setting up the measurements. This flow of chloride resulted in narrower linear ranges, lower slopes, and poorer detection limits due to the mixed responses to acetate and chloride. The degree of deviation from the

Polarity effects in 4-fluoro- and 4-(trifluoromethyl)prolines

• Vladimir Kubyshkin

Beilstein J. Org. Chem. 2020, 16, 1837–1852, doi:10.3762/bjoc.16.151

• [49][50]. The presence of a fluorine-rich group in the structure is also beneficial for the NMR studies based on the detection of the 19F nucleus [51][52][53]. Limited attention has been given to the polarity effects in the proline analogues though. Few studies reported peptides containing proline

Synthesis of 3-substituted isoxazolidin-4-ols using hydroboration–oxidation reactions of 4,5-unsubstituted 2,3-dihydroisoxazoles

• Lívia Dikošová,
• Júlia Laceková,
• Ondrej Záborský and
• Róbert Fischer

Beilstein J. Org. Chem. 2020, 16, 1313–1319, doi:10.3762/bjoc.16.112

• identified as a readily oxidizable polar component by permanganate detection even at room temperature. The prior attempts to cleave the Troc group by zinc dust in acetic acid [42] failed due to the reduction of the N–O bond. Conclusion In summary, we have developed a new synthetic approach towards 3

Synthesis and properties of quinazoline-based versatile exciplex-forming compounds

• Rasa Keruckiene,
• Simona Vekteryte,
• Ervinas Urbonas,
• Matas Guzauskas,
• Eigirdas Skuodis,
• Dmytro Volyniuk and
• Juozas V. Grazulevicius

Beilstein J. Org. Chem. 2020, 16, 1142–1153, doi:10.3762/bjoc.16.101

• 6.2 V could be attributed to energy barriers due to the high ionization potential (6.08 eV) of compound 1 (Figure 7e, inset). A relatively high maximum brightness of 3030 cd/m2 was achieved. Taking into account the rare detection of versatile exciplex-forming properties of compound 1 both with a donor

A smart deoxyribozyme-based fluorescent sensor for in vitro detection of androgen receptor mRNA

• Ekaterina A. Bryushkova,
• Erik R. Gandalipov and
• Julia V. Nuzhina

Beilstein J. Org. Chem. 2020, 16, 1135–1141, doi:10.3762/bjoc.16.100

• types of compounds. It is most promising to develop simple and effective biosensors for the use in situations where traditional methods are not available due to their complexity and laboriousness. In this project, a novel smart deoxyribozyme-based fluorescent sensor for the detection of androgen

• mRNA molecule of the androgen receptor. The constructed sensor is easy to use, has high efficiency and selectivity for the RNA target, and can be reconstructed for the detection of various nucleic acid sequences due to its modular structure. Thus, similar biosensors may be useful for the differential

• electrode, covered by immobilizing enzyme glucose oxidase, for the detection of glucose [1]. A biosensor means a small molecular device that traditionally consists of a bioreceptor (enzyme, cell, aptamer, oligonucleotide, antibody, and other) for the specific recognition of the target molecule and a

Fluorinated phenylalanines: synthesis and pharmaceutical applications

• Laila F. Awad and
• Mohammed Salah Ayoup

Beilstein J. Org. Chem. 2020, 16, 1022–1050, doi:10.3762/bjoc.16.91

• , compared to, for example, magnetic resonance imaging (MRI). PET is particularly well-suited to differentiate neoplastic tissue from non-specific changes induced by chemotherapy treatments [85]. PET is particularly used for the early detection of tumors and metastases, and is an established tool for the

• used in PET due to its relatively long half-life (109 min). In this section we highlight two selected 18FPhe derivatives which are used for PET tumor detection. 4-Borono-2-[18F]fluoro-ᴅ,ʟ-phenylalanine ([18F]FBPA, 70), is a fluorinated derivative of the parent compound designed for boron neutron