A systems-based framework to computationally describe putative transcription factors and signaling pathways regulating glycan biosynthesis

• Theodore Groth,
• Rudiyanto Gunawan and
• Sriram Neelamegham

Beilstein J. Org. Chem. 2021, 17, 1712–1724, doi:10.3762/bjoc.17.119

• termed glycogenes [1][2]. These glycogenes include the glycosyltransferases, glycosidases, sulfotransferases, transporters, etc. The expression of these glycogenes is in turn driven by the action of a class of proteins called transcription factors (TFs). These TFs regulate gene expression by binding

• may regulate pathways related to sialylation, hyaluronan synthesis, as well as chondroitin and dermatan sulfate elongation. Here, STAT1, 4, and 5 proteins were enriched in the IL-21 signaling pathway. Luminal breast cancer types are known to express STAT1 and 3 as well as STATs 2 and 4. STAT5 is known

• [24][25]. It has been found to be upregulated in breast cancer with respect to normal-like. PRDM1, also known as Blimp-1, is a transcriptional repressor, and its upregulation in cancer is known to dysregulate other proteins [26]. The increase poly-LacNAc structures have been shown to play roles in

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

• negative charge on PNA’s backbone. Electrostatic repulsion of the negatively charged phosphates dominates the conformational properties and structure of nucleic acids. In contrast to proteins that prefer to fold in compact structures, DNA and RNA inherently prefer extended conformations that minimize the

• electrostatic repulsion. The maintenance and function of long double-stranded DNA (dsDNA) is achieved through complex mechanisms involving histones and other proteins. Large non-coding RNAs (e.g., ribosomes) manage electrostatic repulsion using positively charged RNA-binding proteins and cations (e.g

• covalent conjugation of PNA to delivery enhancing compounds. Cell-penetrating peptides derived from natural proteins: The initial success of PNA delivery involved PNA conjugates taken up by receptor-mediated endocytosis. Pardridge and co-workers successfully demonstrated in vivo delivery and blood-brain

Antiviral therapy in shrimp through plant virus VLP containing VP28 dsRNA against WSSV

• Santiago Ramos-Carreño,
• Ivone Giffard-Mena,
• Jose N. Zamudio-Ocadiz,
• Alfredo Nuñez-Rivera,
• Ricardo Valencia-Yañez,
• Jaime Ruiz-Garcia,
• Maria Teresa Viana and
• Ruben D. Cadena-Nava

Beilstein J. Org. Chem. 2021, 17, 1360–1373, doi:10.3762/bjoc.17.95

• of interest [12][13][14][15][16]. The antiviral response of RNAi is triggered by double-stranded RNA (dsRNA) to block the synthesis of a specific viral protein, in the case of WSSV the targets being the structural proteins VP19, VP24, VP26, and VP28, as they are involved in cell recognition, virus

• entry, binding and assembly of the virion. Previous studies have shown that silencing these structural proteins in WSSV challenge assays, increases shrimp survival [10][11][17][18][19][20][21]. The VP28 glycoprotein plays an important role in systemic infection by interacting with cell membrane proteins

• , and it is one of the most abundant proteins along with VP26 (≈60%) in the external WSSV surface [21][22]. The RNAi trials using an intramuscular injection (IM) have shown that VP28 glycoprotein is the target of choice to block WSSV infection in shrimp [14][23][24]. However, RNAi intramuscular (IM

Icilio Guareschi and his amazing “1897 reaction”

• Gian Cesare Tron,
• Alberto Minassi,
• Giovanni Sorba,
• Mara Fausone and
• Giovanni Appendino

Beilstein J. Org. Chem. 2021, 17, 1335–1351, doi:10.3762/bjoc.17.93

• work is testified by Willstätter, who in his memoirs refers to Guareschi as “alkaloid chemist” [28]. Ptomaines (from the Greek πτωμα, cadaver) are anaerobic bacterial degradation products of proteins and choline-containing phospholipids. The formation of these is associated with putrefaction of animal

A new glance at the chemosphere of macroalgal–bacterial interactions: In situ profiling of metabolites in symbiosis by mass spectrometry

• Marine Vallet,
• Filip Kaftan,
• Veit Grabe,
• Fatemeh Ghaderiardakani,
• Simona Fenizia,
• Aleš Svatoš,
• Georg Pohnert and
• Thomas Wichard

Beilstein J. Org. Chem. 2021, 17, 1313–1322, doi:10.3762/bjoc.17.91

• is an important part of the MALDI-MSI experiment. MALDI-MS can be used to identify proteins and metabolic signatures [22][23][24] from bacteria and microalgae, as well as biofilms [25]. The primary function of the applied matrix is to improve the quality of the MS spectra, particularly the signal

Synthesis of multiply fluorinated N-acetyl-D-glucosamine and D-galactosamine analogs via the corresponding deoxyfluorinated glucosazide and galactosazide phenyl thioglycosides

• Vojtěch Hamala,
• Lucie Červenková Šťastná,
• Martin Kurfiřt,
• Petra Cuřínová,
• Martin Dračínský and
• Jindřich Karban

Beilstein J. Org. Chem. 2021, 17, 1086–1095, doi:10.3762/bjoc.17.85

• . Keywords: amino sugars; deoxyfluorination; fluorinated carbohydrates; hexosamine hemiacetals; thioglycosides; Introduction Fluorinated carbohydrates are versatile carbohydrate mimetics used to probe or manipulate the recognition of carbohydrates by carbohydrate-binding proteins or carbohydrate-processing

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

• , replication, splicing and other fundamental processes in biological information transfer. More specifically, they can affect chemical and thermodynamic stability, folding, secondary and tertiary structure, activity and interactions between nucleic acids, proteins and receptors. Particularly, as far as

• production of proteins, enzymes and receptors that may be inhibited by small-molecule and antibody therapeutics. However, native RNA oligonucleotides do not possess sufficient metabolic stability for in vivo applications. Therefore, chemical modification is absolutely essential to re-engineer RNA into a

• targeted to proviral HIV DNA [68], and as a triplex-forming oligonucleotide that selectively binds a sequence within the chromatin structure of cell nuclei [69]. Remarkably, 3'-NP DNA can also act as an RNA mimic in interactions with binding proteins despite lacking a ribose moiety, making them useful

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

• of the nature of the target proteins. CCR5, a cell surface receptor, is internalized upon ligand binding before recycling back to the cell surface or processed for degradation in the lysosome [34]. On the other hand, gp120 is a viral surface protein that is involved in viral entry through

Synthetic reactions driven by electron-donor–acceptor (EDA) complexes

• Zhonglie Yang,
• Yutong Liu,
• Kun Cao,
• Xiaobin Zhang,
• Hezhong Jiang and
• Jiahong Li

Beilstein J. Org. Chem. 2021, 17, 771–799, doi:10.3762/bjoc.17.67

• construction of C–S bonds C–S bonds are commonly present in amino acids, proteins, glycosides, nucleic acids, and other biological macromolecules. In recent years, photocatalyst- and transition-metal strategies have been employed to construct C–S bonds [66][67][68][69]. The C–S bond synthesis via EDA-complex

DNA with zwitterionic and negatively charged phosphate modifications: Formation of DNA triplexes, duplexes and cell uptake studies

• Yongdong Su,
• Maitsetseg Bayarjargal,
• Tracy K. Hale and
• Vyacheslav V. Filichev

Beilstein J. Org. Chem. 2021, 17, 749–761, doi:10.3762/bjoc.17.65

• recognise and cut DNA sequences, or CRISPR-CAS9 [8][9][10] and CAS9-constructs [11][12][13][14] which rely on large proteins to open the target duplex, triplex-forming oligonucleotides (TFOs) [15] can be designed to bind in a sequence-specific manner to double-stranded DNA (dsDNA) [16]. In forming the

Valorisation of plastic waste via metal-catalysed depolymerisation

• Francesca Liguori,
• Carmen Moreno-Marrodán and
• Pierluigi Barbaro

Beilstein J. Org. Chem. 2021, 17, 589–621, doi:10.3762/bjoc.17.53

• oxidation, cross-linkage, bond cleavage). The term “biodegradation” indicates a “degradation caused by enzymatic processes resulting from the action of cells”. Although commonly used, also for artificial polymers, the term “biodegradable” specifically refers to biorelated polymers (i.e., proteins, nucleic

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

• , which involves the use of targeting ligands, such as monoclonal antibodies, antibody fragments, proteins, peptides, and other small molecules, including vitamins and carbohydrates [7][8]. The targeting ligands are coupled to the surface of the carrier to selectively target tumor cells that overexpress a

Biochemistry of fluoroprolines: the prospect of making fluorine a bioelement

• Vladimir Kubyshkin,
• Rebecca Davis and
• Nediljko Budisa

Beilstein J. Org. Chem. 2021, 17, 439–460, doi:10.3762/bjoc.17.40

• structure and distinct conformational profile, proline is unique in the repertoire of the 20 amino acids coded into proteins. Here, we summarize the biochemical work on the replacement of proline with (4R)- and (4S)-fluoroproline as well as 4,4-difluoroproline in proteins done mainly in the last two decades

• proline replacements are able to elevate the protein expression speed and yields and improve the thermodynamic and kinetic folding profiles of individual proteins. In this context, fluoroprolines can be viewed as useful tools in the biotechnological toolbox. As a prospect, we envision that proteome-wide

• biodiversity, containing fluorine as a bioelement. Keywords: amino acids; evolution; fluorine; proline; proteins; Introduction Nature employs a rather small set of chemical elements for constructing the core biochemical makeup. Most elements of the periodic table are excluded from the biochemical world. Not

Synthesis of legonmycins A and B, C(7a)-hydroxylated bacterial pyrrolizidines

• Wilfred J. M. Lewis,
• David M. Shaw and
• Jeremy Robertson

Beilstein J. Org. Chem. 2021, 17, 334–342, doi:10.3762/bjoc.17.31

• ]. Proteins coded by three of these genes (LgnA, LgnB, and LgnD) were shown to assemble legonindolizidines A (1) and B (2) – from proline, threonine, and a fatty acid component – which are then converted by LgnC, a flavin-dependent monooxygenase, into the corresponding legonmycins (3 and 4) via a sequence of

• was established with, in this case, PxaB achieving the oxidative steps from indolizidine intermediates 5–8 produced by PxaA. An important aspect of this work was the finding that at least 90 different bacterial strains, spanning 23 species, contain gene sequences encoding proteins related to PxaB

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

• fluorinated probes and their incorporation into macromolecules, the application of 19F NMR to monitor protein–protein interactions, protein–ligand interactions, physiologically relevant ions and in the structural analysis of proteins and nucleic acids. The continued relevance of the technique to investigate

• labelling 19F NMR offers an attractive option for investigating the interactions between proteins and other biomolecules such as nucleic acids. Many of the advantages of 19F NMR have already been discussed but it is worth highlighting that it is a particularly useful technique to study large proteins that

• cannot easily be probed by conventional NMR experiments. Given that fluorine atoms (e.g., 19F labels) are not naturally present in proteins, a key element to establishing 19F NMR in this area has been the development of methods that can be used to give access to 19F-labelled proteins. Methods for the

The preparation and properties of 1,1-difluorocyclopropane derivatives

• Kymbat S. Adekenova,
• Peter B. Wyatt and
• Sergazy M. Adekenov

Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25

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

• design. Protein–protein interactions and their discovery are thus an interesting avenue for understanding how protein complexes, which make up the majority of proteins, work. Keywords: characterisation methods; heterooligomeric complex; homooligomeric complex; molecular interactions; protein–protein

• interactions; Introduction From signalling over transport to catalysis, the broad functionality of proteins is essential in the cellular machinery. To this effect, proteins can be seen as the workforce of the cell. Proteins relay some of their functionality via interactions between protein nodes called

• protein–protein interactions (PPIs). Hedin characterised the first PPI with trypsin and antitrypsin in 1906 [1], which provided a landmark for the awareness of what role PPIs have in cellular physiology. In fact, even though individual proteins perform essential functions, their effectiveness in the cell

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

• separation of glycopeptides in RPLC is mainly driven by the peptide portions. Thus, information on different proteins and glycosylation sites appears in the form of glycopeptide clusters. Next to the peptide portion, glycosylation features, such as sialic acids, can strongly influence the retention time [8

• this, a sample containing immunoglobulins G and A (IgG and IgA), simultaneously captured from human plasma, was chosen. This sample showed a considerable level of complexity due to the presence of multiple glycoproteins of interest and cocaptured (glyco)proteins from the plasma. The tools included

• by Byonic The automated and score-based MS/MS glycopeptide identification using Byonic resulted in the confident assignment of ten IgG/IgA N-glycopeptide clusters of interest (Table 1 and Figures S1–S10, Supporting Information File 2). Assigned glycopeptides from copurified human plasma proteins

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

• (“control”). The error bars represent the standard error. N ≥ 5 (control and surfactin-treated assays), N = 2 (MeOH-treated assays). Overview on the biosynthetic pathways of surfactin (A), plipastatin (B), and bacillaene (C) produced by B. subtilis. The lightning bolt indicates the proteins for which the

Selected peptide-based fluorescent probes for biological applications

• Debabrata Maity

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

• ). Fluorescence resonance energy transfer (FRET) relies on the distance-dependent transfer of energy from a donor fluorophore to an acceptor fluorophore. Genetically encoded fluorophores, such as green fluorescent protein (GFP) and related blue, cyan, yellow and red fluorescent proteins have provided the ability

• important biomolecules including nucleotides, DNA, proteins, lipids etc. in aqueous media. Fluorescent peptides have also been used for specific organelles such as lysosomes tracking. In this review, it is summarized Schmuck group’s tremendous effort in developing fluorescent peptide-based probes for

• insulin Schmuck and co-workers reported a supramolecular ensemble in combination of a pyrene-tagged amphiphilic peptide beacon (6) and a macrocyclic host (cucurbit[8]uril, CB[8]) for ratiometric fluorescent detection of amino acid derivatives, specific peptides, and proteins in aqueous media (Figure 6

UV resonance Raman spectroscopy of the supramolecular ligand guanidiniocarbonyl indole (GCI) with 244 nm laser excitation

• Tim Holtum,
• Vikas Kumar,
• Daniel Sebena,
• Jens Voskuhl and
• Sebastian Schlücker

Beilstein J. Org. Chem. 2020, 16, 2911–2919, doi:10.3762/bjoc.16.240

• , Universitätsstrasse 7, 45141 Essen, Germany 10.3762/bjoc.16.240 Abstract Ultraviolet resonance Raman (UVRR) spectroscopy is a powerful vibrational spectroscopic technique for the label-free monitoring of molecular recognition of peptides or proteins with supramolecular ligands such as guanidiniocarbonyl pyrroles

• UVRR approach from peptides to proteins as binding partners for GCPs is the UV-excited autofluorescence from aromatic amino acids observed for laser excitation wavelengths >260 nm. These excitation wavelengths are in the electronic resonance with the GCP for achieving both a signal enhancement and the

• the results from density functional theory (DFT) calculations. Keywords: GCI; GCP; guanidiniocarbonyl indole; guanidiniocarbonyl pyrrole; UVRR; Raman spectroscopy; resonance Raman; Introduction Supramolecular ligands are capable to selectively bind to peptides and proteins via reversible non

Incorporation of a metal-mediated base pair into an ATP aptamer – using silver(I) ions to modulate aptamer function

• Marius H. Heddinga and
• Jens Müller

Beilstein J. Org. Chem. 2020, 16, 2870–2879, doi:10.3762/bjoc.16.236

• function opens new possibilities for applications of oligonucleotides. Keywords: aptamer; ATP; bioinorganic chemistry; DNA; imidazole; metal-mediated base pairs; Introduction Aptamers are oligonucleotides capable of recognizing and binding to specific molecules up to the size of proteins [1]. While

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

• cytosine (C) [2]. Similarly, proteins, like microtubules and actin filaments, are self-sorted on the molecular level in living cells [3]. Furthermore, the smaller molecules of life such as sugars [4], peptides, and fatty acids [5] undergo self-sorting in the construction of a cell [6][7]. The above

• activity in a Knoevenagel addition reaction. At the same time, the click reaction remained shut down (ON-1, OFF-2). In sum, the three interdependent states SelfSORT-I to III regulated two different reaction outcomes and an OFF state. In biology, motor proteins carry out essential tasks by walking along

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

• -hydroxyoctadecanoic and stearic acids as well as (E)-2-octadecenoic acids are obtained similarly directly from palmitic acid. The proposed biosynthesis likely takes place in form of the conjugated acids, e.g., coenzyme A esters or acyl carrier proteins. Finally, the acids are converted into the isoprenyl esters and

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

• of cell-surface receptors to extracellular signals, such as small molecules or proteins. In recent years, there has been considerable interest in modifying cells with artificial receptors, as a means to provide them with new properties [1]. We have recently reported a method for decorating His-tagged

• cell surface proteins with self-assembled synthetic receptors based on modified DNA duplexes [2] (Figure 1A). One of the oligodeoxynucleotides (ODNs) constituting the artificial receptors (ODN-1) is appended with a trinitrilotriacetic acid group (tri-NTA) that was developed by our group [3] and can

• approach can be used to fluorescently label the His-tagged proteins with different colors, simply by changing the dye (Y) on Y-ODN-2. An interesting difference between the synthetic and the natural cell surface receptors, which is in the focus of this study, is that the number of artificial receptors per