How and why plants and human N-glycans are different: Insight from molecular dynamics into the “glycoblocks” architecture of complex carbohydrates

• Carl A. Fogarty,
• Aoife M. Harbison,
• Amy R. Dugdale and
• Elisa Fadda

Beilstein J. Org. Chem. 2020, 16, 2046–2056, doi:10.3762/bjoc.16.171

• , implicated in protein folding and structural stability, and mediating interactions with receptors and with the environment. All N-glycans share a common core from which linear or branched arms stem from, with functionalization specific to different species and to the cells’ health and disease state. This

• ][21][22][23]. More specifically, we investigate how core α(1-3)-linked fucose (Fuc) and β(1-2)-linked xylose (Xyl) affect the structure and dynamics of plants N-glycoforms [23] and of hybrid constructs with mammalian N-glycoforms [24]. At first glance plants protein N-glycosylation [23] is quite

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

• Information File 1) of galectin-1, a β-sheet lectin protein that is available in bovine spleen [53] (for a detailed crystal structure see the Protein Data Bank; PDB ID 1SLT). Given the amphiphilic and pH-responsive nature of PEP-1, we investigated both the pH- and concentration-dependent formation of

• (Glu−) amino acids [73][74]. Mechanistic insights into the observed conformational transformation via molecular dynamics simulations are underway in our laboratory. Conclusion In summary, we synthesized a naturally occurring amphiphilic peptide fragment, PEP-1, from a β-sheet lectin protein, galectin-1

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

• efficient delivery of a model protein (avidin, around 67 kDa) into cells through biotin–avidin technology could be achieved in the presence of this strikingly small peptide. However, the uptake of peptide 9-labeled avidin was dramatically reduced into cells that express less GAGs on the cell surfaces. These

• added to minimize the passive diffusion across the membrane and to maximize the solubility in water. Biotin was used to interface the transporter and streptavidin to probe the COC-mediated protein delivery. A chloroalkane, finally, was needed for the HC CAPA. The trifunctional transporter 23 was first

• complexed with streptavidin 24 (Figure 6). The resulting complex 25 was then incubated with HGM cells. These are stable cell lines, expressing the self-labeling HaloTag protein and GFP in the outer mitochondrial membrane (Figure 6a) [55]. If the complex 25 indeed reaches the cytosol, the chloroalkane will

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

• this protein-inspired architecture have recently been praised in the use of naphthotubes [3]. Association between the receptor and the analyte may change considerably when the receptor is attached to an electrode surface or embedded in a sensor membrane. Water, as the most common environment for real

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

• issues in the chemistry of amino acids, while the latter are key actors in multiple biochemical processes. In protein translation, for example, 20 (+2) amino acids are utilized for polymerizing them into a primary structure of a protein. Most of these structures share the same key elements with the

• analogues with distinct hydrophobic properties can impact their ability to pass biomembranes [54][55][56]. A crystallographic study has shown that when included into a protein structure, a fluorine atom exhibits a network of interaction within a protein core [57]. Another recent study showed that the

• protein chemistry. The peptide bond can exist in two discrete states, commonly designated as trans- and cis-rotamers (ω = 180 and 0°, respectively). The cis-peptide bond is very rare in natural proteins [79], except for the cases when it precedes a proline residue. The secondary amino group of proline

Nonenzymatic synthesis of anomerically pure, mannosyl-based molecular probes for scramblase identification studies

• Giovanni Picca,
• Markus Probst,
• Simon M. Langenegger,
• Oleg Khorev,
• Peter Bütikofer,
• Anant K. Menon and
• Robert Häner

Beilstein J. Org. Chem. 2020, 16, 1732–1739, doi:10.3762/bjoc.16.145

• Bern, Switzerland Department of Biochemistry, Weill Cornell Medical College, 1300 York Avenue, 10065 New York, United States of America 10.3762/bjoc.16.145 Abstract The chemical synthesis of molecular probes to identify and study membrane proteins involved in the biological pathway of protein

• glycolipid analogs; scramblase; Introduction Mannosyl phosphoryl dolichol (MPD), an important, multifunctional glycolipid, is used as a mannose donor for protein N-glycosylation, O- and C-mannosylation, and glycosylphosphatidylinositol (GPI) anchoring in the luminal leaflet of the endoplasmic reticulum (ER

• ) [1][2][3][4][5][6][7][8]. Interestingly, MPD is synthesized on the cytoplasmic face of the ER and must be translocated across the ER membrane to participate in luminal glycosyltransfer reactions [3][4]. A specific membrane protein – MPD scramblase – is required to facilitate the transbilayer movement

Synthesis of Streptococcus pneumoniae serotype 9V oligosaccharide antigens

• Sharavathi G. Parameswarappa,
• Claney L. Pereira and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2020, 16, 1693–1699, doi:10.3762/bjoc.16.140

• acetate loss during isolation, purification, or protein conjugation leads to structurally altered CPS. Vaccines based on synthetic carbohydrate antigens [11][12][13][14][15] such as the first commercially available semisynthetic glycoconjugate vaccine Quimi Hib® against H. influenzae [16] and Shigella

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

• 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

Synthesis of new dihydroberberine and tetrahydroberberine analogues and evaluation of their antiproliferative activity on NCI-H1975 cells

• Giacomo Mari,
• Lucia De Crescentini,
• Serena Benedetti,
• Francesco Palma,
• Stefania Santeusanio and
• Fabio Mantellini

Beilstein J. Org. Chem. 2020, 16, 1606–1616, doi:10.3762/bjoc.16.133

• effects [32], inhibits both hERG current and the expression of hERG protein [33], inhibits the pancreatic lipase [34], shows antiradical, revitalizing and antifibrotic properties for dermatological applications [35], manifests a synergic effect with antibiotics [36], and displays antitumoral activities

• proliferation as evaluated by SRB assay (estimating total protein content) at 24 h and 48 h of treatment. Data are expressed as mean ± SD (n = 3). *p < 0.05 vs CTR (DMSO 0.05%). Preparation of functionalized-BER, -DHBER and -THBER derivatives. Substrate scope of hydrazono-DHBER. Reaction conditions: DHBER (1.0

Antibacterial scalarane from Doriprismatica stellata nudibranchs (Gastropoda, Nudibranchia), egg ribbons, and their dietary sponge Spongia cf. agaricina (Demospongiae, Dictyoceratida)

• Cora Hertzer,
• Stefan Kehraus,
• Nils Böhringer,
• Fontje Kaligis,
• Robert Bara,
• Dirk Erpenbeck,
• Gert Wörheide,
• Till F. Schäberle,
• Heike Wägele and
• Gabriele M. König

Beilstein J. Org. Chem. 2020, 16, 1596–1605, doi:10.3762/bjoc.16.132

• were shown to share and cover various core functions of sponge metabolism by functionally equivalent symbionts, analogous enzymes, or biosynthetic pathways [16][79][80]. Another Spongia species, S. officinalis, was shown to harbour bacteria with terpenoid cyclases/protein prenyltransferases responsible

Heterogeneous photocatalysis in flow chemical reactors

• Christopher G. Thomson,
• Ai-Lan Lee and
• Filipe Vilela

Beilstein J. Org. Chem. 2020, 16, 1495–1549, doi:10.3762/bjoc.16.125

Synthesis of new fluorescent molecules having an aggregation-induced emission property derived from 4-fluoroisoxazoles

• Kazuyuki Sato,
• Akira Kawasaki,
• Yukiko Karuo,
• Atsushi Tarui,
• Kentaro Kawai and
• Masaaki Omote

Beilstein J. Org. Chem. 2020, 16, 1411–1417, doi:10.3762/bjoc.16.117

• bioprobes [9][10][11][12][13][14]. For example, it is presumed that prion disease, which is caused by the accumulation of prion protein aggregates in the brain, plays an important role in the pathophysiological mechanism of prion protein-polymerized oligomers. However, since prion protein oligomers cannot

Synthesis, antiinflammatory activity, and molecular docking studies of bisphosphonic esters as potential MMP-8 and MMP-9 inhibitors

• Abimelek Cortes-Pacheco,
• María Adelina Jiménez-Arellanes,
• Francisco José Palacios-Can,
• José Antonio Valcarcel-Gamiño,
• Rodrigo Said Razo-Hernández,
• María del Carmen Juárez-Vázquez,
• Adolfo López-Torres and
• Oscar Abelardo Ramírez-Marroquín

Beilstein J. Org. Chem. 2020, 16, 1277–1287, doi:10.3762/bjoc.16.108

• was pointing away from the zinc ion [39]. The calculated distances from the Zn2+ ion and the different sites at the ligand and the protein are summarized in Table 5. The zinc chelation in MMP-9 occurred in a different way. The predicted orientation of the histidine residues at the catalytic site were

• not aiming directly at the metal ion. However, it can be assumed that because of the flexibility of the protein in solution, the coordination to the metal ion would be possible. The targets 3 and 4 could coordinate the Zn2+ ion through the oxygen atom double bonded to the phosphorus atom (P=O) of one

• molecules inside the catalytic site allowed the coordination through the ester groups rather than through the phosphonate moieties. The calculated distances from the Zn2+ ion and the different sites at the ligand and the protein are summarized in Table 6. In Figure 4, a schematic representation of the

Anthelmintic drug discovery: target identification, screening methods and the role of open science

• Frederick A. Partridge,
• Ruth Forman,
• Carole J. R. Bataille,
• Graham M. Wynne,
• Marina Nick,
• Angela J. Russell,
• Kathryn J. Else and
• David B. Sattelle

Beilstein J. Org. Chem. 2020, 16, 1203–1224, doi:10.3762/bjoc.16.105

• researchers, The Worm Breeder’s Gazette, which combines advice and suggestions on methods with informal communication of new findings in advance of publication. For example, the Nobel prize-winning use of a green fluorescence protein as a marker was reported in the Gazette by Martin Chalfie and colleagues

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

• currently described 18 alternative splice variants of AR mRNA – AR-FL, AR45, AR-23, AR V1-V14 and AR-8. Most of them encode small-sized or functionally inactive proteins [16]. However, all translated isoforms of the AR protein contain NTD, which is critical for AR function. This is the main reason to target

Synthesis of esters of diaminotruxillic bis-amino acids by Pd-mediated photocycloaddition of analogs of the Kaede protein chromophore

• Esteban P. Urriolabeitia,
• Pablo Sánchez,
• Alexandra Pop,
• Cristian Silvestru,
• Eduardo Laga,
• Ana I. Jiménez and
• Carlos Cativiela

Beilstein J. Org. Chem. 2020, 16, 1111–1123, doi:10.3762/bjoc.16.98

• complexes 4. Treatment of 4 with CO in a MeOH/NCMe mixture promoted the methoxycarbonylation of the palladated carbon and the release of the corresponding ortho-functionalized 1,3-diaminotruxillic bis-amino esters 5 as single isomers. Keywords: amino acids; C–H activation; Kaede protein; oxazolones

• precursors of the photoconvertible chromophore of the Kaede protein, an imidazolone with outstanding photophysical properties [31][32][33][34][35][36][37][38]. It is clear from Figure 2b that the molecular skeleton contains different reactive functional groups, which offer a variety of structural

• findings were also confirmed by analysis of the 13C NMR spectra. Conclusion The synthesis of cyclobutane 1,3-diaminotruxillic bis-amino acids has been achieved with full stereoselectivity (ε-isomer) starting from polyfunctional oxazolones 2 derived from the chromophore of the Kaede protein in three steps

A cyclopeptide and three oligomycin-class polyketides produced by an underexplored actinomycete of the genus Pseudosporangium

• Shun Saito,
• Kota Atsumi,
• Tao Zhou,
• Keisuke Fukaya,
• Daisuke Urabe,
• Naoya Oku,
• Md. Rokon Ul Karim,
• Hisayuki Komaki and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2020, 16, 1100–1110, doi:10.3762/bjoc.16.97

• consisting of glucose 0.5%, glycerol 2%, soluble starch 2%, Pharmamedia (Traders Protein) 1.5%, dry yeast (Kamaishi Hamayuri Yeast, Nihon Tensai Seito Co., Ltd.) 0.3%. The pH of the medium was adjusted to 7.0 before sterilization. The inoculated flasks were placed on a rotary shaker TB98 (Takasaki Scientific

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

• the properties of peptides and proteins [5][6][7], influencing aspects such as protein folding, protein–protein interactions, ribosomal translation, lipophilicity, acidity/basicity, optimal pH, stability, thermal stability, and therapeutic properties [8][9][10]. This extends to metabolic properties of

• , especially in therapeutic proteins and peptide-based vaccines [18]. Enhanced catabolic stability [6] can arise from the role of particular aromatic amino acids in membrane–protein interactions [19]. Furthermore, fluorinated aromatic amino acids can alter enzymatic activity as a result of enhanced protein

• protein–protein and protein–ligand interactions and consequently metabolic processes [20][21]. Fluorinated phenylalanines (FPhe) have been incorporated into various proteins and enzymes [22][23][24][25] with advantageous biophysical, chemical, and biological properties, and their effect on the stability

Fabclavine diversity in Xenorhabdus bacteria

• Sebastian L. Wenski,
• Harun Cimen,
• Natalie Berghaus,
• Sebastian W. Fuchs,
• Selcuk Hazir and
• Helge B. Bode

Beilstein J. Org. Chem. 2020, 16, 956–965, doi:10.3762/bjoc.16.84

• fcl BGCs in Xenorhabdus and Photorhabdus strains, several candidate clusters were identified, which were conserved both in their BGC synteny as well as at the single protein level (Figure 2) [22]. The strain KK7.4 showed protein identities of ≥95% with X. stockiae and strain KJ12.1 (Figure S1

• originally also contained the NRPS-PKS-hybrid genes (Figure 2) [22]. In contrast, the BGC of P. temperata is reduced to only harbor the homologous genes of fclC, fclD and fclE (Figure 2) [22]. X. innexi also harbors a fcl-like BGC, with protein identities of 68–90% compared to X. stockiae (Figure S1

Design and synthesis of diazine-based panobinostat analogues for HDAC8 inhibition

• Sivaraman Balasubramaniam,
• Sajith Vijayan,
• Liam V. Goldman,
• Xavier A. May,
• Kyra Dodson,
• Sweta Adhikari,
• Fatima Rivas,
• Davita L. Watkins and
• Shana V. Stoddard

Beilstein J. Org. Chem. 2020, 16, 628–637, doi:10.3762/bjoc.16.59

• involve acetylation/deacetylation of histone proteins by histone deacetylases (HDACs) [1]. HDACs belong to an important family of enzymes consisting of 18 isozymes. They control protein acetylation, which is a change that occurs after translation. In addition, they regulate gene transcription, cell

• Biotek Synergy HTX multimodal plate reader after incubation for 30 minutes. Preparation of the HDAC8 receptor for docking The HDAC8 crystal structure (protein database pdb: 1W22) [32] was utilized as the docking receptor for all compounds. This receptor is crystalized as a dimer thus only the A chain was

Opening up connectivity between documents, structures and bioactivity

• Christopher Southan

Beilstein J. Org. Chem. 2020, 16, 596–606, doi:10.3762/bjoc.16.54

• “D“ where a bioactivity “A” with a quantitative result “R” (e.g., an IC50) is reported for chemical structure “C” that modulates (e.g., inhibits) a protein target “P”. A useful shorthand for this connectivity thus becomes DARCP. The problem at the core of this article is that the community has spent

• . However, we will need to await the technical applicability in respect to DARCP capture to see if this opens up connectivity. Keywords: activity data; databases; drug discovery; chemical structures; protein targets; Introduction This article assesses a key aspect of data sharing that has the potential to

• Google and indexed for chemistry searching [4][5]. Structures: A necessary focus of this article will be traditional small-molecule chemistry that is not too far outside the rule-of-five lead-like property space. In terms of connectivity antibodies, other protein biotherapeutics, as well as large

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

Two antibacterial and PPARα/γ-agonistic unsaturated keto fatty acids from a coral-associated actinomycete of the genus Micrococcus

• Amit Raj Sharma,
• Enjuro Harunari,
• Naoya Oku,
• Nobuyasu Matsuura,
• Agus Trianto and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2020, 16, 297–304, doi:10.3762/bjoc.16.29

• incubated at 30 °C on a rotary shaker at 200 rpm for two days. Three mL each of the seed culture were inoculated into 29 500 mL K-1 flasks containing 100 mL of A16 production medium, which consisted of glucose 2%, Pharmamedia (Traders Protein, Memphis, TN, USA) 1%, CaCO3 0.5%, Diaion HP-20 (Mitsubishi

Synthesis and herbicidal activities of aryloxyacetic acid derivatives as HPPD inhibitors

• Man-Man Wang,
• Hao Huang,
• Lei Shu,
• Jian-Min Liu,
• Jian-Qiu Zhang,
• Yi-Le Yan and
• Da-Yong Zhang

Beilstein J. Org. Chem. 2020, 16, 233–247, doi:10.3762/bjoc.16.25

• balance of the plant, which interrupts nucleic-acid and protein metabolism, and is especially effective in broadleaf weeds, such as Amaranthus retroflexus and Alfalfa. The application of 2,4-D causes excessive growth that ultimately results in plant death. Consequently, 2,4-D has become one of the world’s

• docking study was conducted with the method reported previously [10][19][32][33][34]. Crystal structures of Arabidopsis thaliana HPPD (PDB ID: 1TFZ) with the native ligand, named DAS869 were downloaded from the Protein Data Bank. The docking was carried out using Discovery Studio 4.0. During the docking

• process, all water molecules were removed. The ligand and protein were prepared with the Dock Ligands tool before docking. By using Define and Edit Binding Site tool to identify the active site. Then the center of the native ligand was deleted. Utilizing the CDOCKER, the prepared ligand was docked into

Combination of multicomponent KA² and Pauson–Khand reactions: short synthesis of spirocyclic pyrrolocyclopentenones

• Riccardo Innocenti,
• Elena Lenci,
• Gloria Menchi and
• Andrea Trabocchi

Beilstein J. Org. Chem. 2020, 16, 200–211, doi:10.3762/bjoc.16.23

• molecular scaffolds to develop chemical libraries can increase the chance of finding compounds able to address the so-called “undruggable” targets, such as protein–protein interactions [1]. In this context, molecules containing one or more rings are of primary interest, as they will suffer a reduced

• conformational entropy penalty upon binding to a protein target, and the approach of constraining the ligand conformation with a ring is widely used in drug design [2]. Accordingly, with increasing interest for sp3-rich molecules, spirocyclic compounds are being considered valuable as molecular platforms for the

• generation of high-quality small molecule collections, taking advantage of the stereochemical diversity, and of their three-dimensional shape and structural bias to develop lead compounds, specifically in the field of protein–protein interactions [3][4][5][6]. Spiranic rings such as spiroketals are present