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

• helminths, but that the rate of drug discovery has been very low, so efforts must be made to enhance cooperation among the various groups pursuing this strategy [83]. They go on to suggest that sharing of both positive and negative screening data via online databases is a priority to focus attention on the

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

• our SDFS on the sequence inside the first exon. Although splice variants of AR-FL (full-size molecule), AR-V7, and AR-V9 [17][18] are the most important ones from a clinical point of view, we analyzed all nucleotide sequences of the translated AR mRNAs from open databases (Supporting Information File

Opening up connectivity between documents, structures and bioactivity

• Christopher Southan

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

• millions effectively burying these relationships in PDFs over many decades but must now spend millions more trying to get them back out. The key imperative for this is to increase the flow into structured open databases. The positive impacts will include expanded data mining opportunities for drug

• in minutes. Unfortunately, no journals have yet instigated a flow of author-specified DARCP directly into open databases. Progress may come from trends such as open science, open access (OA), findable, accessible, interoperable and reusable (FAIR), resource description framework (RDF) and WikiData

• . 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

Isolation of fungi using the diffusion chamber device FIND technology

• Benjamin Libor,
• Henrik Harms,
• Stefan Kehraus,
• Ekaterina Egereva,
• Max Crüsemann and
• Gabriele M. König

Beilstein J. Org. Chem. 2019, 15, 2191–2203, doi:10.3762/bjoc.15.216

• comparison (BLAST) of DNA sequences (ITS1, ITS2, 18S, 5.8S, 28S, RPBII, tef1α and β-tubulin) with reference sequences deposited in public databases (GenBank) and microscopical analysis of morphological characteristics, identified 12 ascomycetes from 12 different genera. Except for Scopulariopsis brevicaulis

Stereochemical investigations on the biosynthesis of achiral (Z)-γ-bisabolene in Cryptosporangium arvum

• Jan Rinkel and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2019, 15, 789–794, doi:10.3762/bjoc.15.75

• was isolated and identified by one- and two dimensional NMR spectroscopy (Table S2, Supporting Information File 1), EIMS databases and GC retention index as the known sesquiterpene (Z)-γ-bisabolene (5). Because the two olefinic carbon atoms of its quaternary double bond could not be unambiguously

Back to the future: Why we need enzymology to build a synthetic metabolism of the future

• Tobias J. Erb

Beilstein J. Org. Chem. 2019, 15, 551–557, doi:10.3762/bjoc.15.49

• million proteins were deposited into protein sequence databases, such as UniProtKB [29]. More than 40,000 enzymes were biochemically characterized and the corresponding data is available in specialized enzyme databases, such as BRENDA [30]. This wealth of biological information provides a good starting

• point to search for enzyme variants that possess a desired catalytic activity. While existing databases might provide a good resource to find the parts to reconstruct level 3 pathways, this task becomes more challenging in respect to level 4 and level 5 designs that require new-to-nature reactions. How

• protein sequence and enzyme databases for suitable candidates is key to advance metabolic retrosynthesis. However, there are still some practical issues in extracting the necessary information from different databases. One particular problem of sequence databases like UniProtKB is the high number of

Adhesion, forces and the stability of interfaces

• Robin Guttmann,
• Johannes Hoja,
• Christoph Lechner,
• Reinhard J. Maurer and
• Alexander F. Sax

Beilstein J. Org. Chem. 2019, 15, 106–129, doi:10.3762/bjoc.15.12

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

• spectra often reveal key structural features. Furthermore, the availability of large cross-platform databases useful for dereplication allows focussing on new compounds. We are interested in natural compounds from Roseobacter group bacteria, an abundant class of marine bacteria occurring in diverse

Protein–protein interactions in bacteria: a promising and challenging avenue towards the discovery of new antibiotics

• Laura Carro

Beilstein J. Org. Chem. 2018, 14, 2881–2896, doi:10.3762/bjoc.14.267

• form the binding pocket (Figure 4) [58][59]. Utilizing a virtual screening of two different databases (i.e., the National Cancer Institute [60] and an in-house collection of 32,000 compounds), Wijfells et al. were able to identify a small-molecule mimic of the des-amino-Leu-Phe (dLF) component of the

Volatiles from the tropical ascomycete Daldinia clavata (Hypoxylaceae, Xylariales)

• Tao Wang,
• Kathrin I. Mohr,
• Marc Stadler and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2018, 14, 135–147, doi:10.3762/bjoc.14.9

• significant activities against competing microbes, but the volatile profiles of these biocontrol candidates were only evaluated using databases like NIST, which can only serve to detect and identify known compounds. The current study demonstrates the need of chemical synthesis for rigorous identification of

Sulfation and amidinohydrolysis in the biosynthesis of giant linear polyenes

• Hui Hong,
• Markiyan Samborskyy,
• Katsiaryna Usachova,
• Katharina Schnatz and
• Peter F. Leadlay

Beilstein J. Org. Chem. 2017, 13, 2408–2415, doi:10.3762/bjoc.13.238

• that the Slf protein sequence might be a useful probe to uncover further examples of strains producing these or closely-related compounds. BLAST analysis of public databases using the protein sequence of the Slf of DSM4137 as a probe sequence uncovered multiple candidate Slf sequences (see sequence

• before or after the specific sulfonation step. The sequence of the sulfotransferase is a useful probe to uncover related gene clusters in public sequence databases. Sulfonation remains a rare and relatively poorly understood modification in natural product biosynthesis [27][28][29][30]. As our

Expression, purification and structural analysis of functional GABA transporter 1 using the baculovirus expression system

• Jing Hu,
• Chris Weise,
• Christoph Böttcher,
• Hua Fan and
• Jian Yin

Beilstein J. Org. Chem. 2017, 13, 874–882, doi:10.3762/bjoc.13.88

• peptides from primary sequence databases with Mascot (http://www.matrixscience.com/). The biological function of recombinant proteins of mammalian origin expressed in insect cells may be altered by different N-glycan status. We observed that the terminal sialic acid residues are essential for the GABA

Opportunities and challenges for the sustainable production of structurally complex diterpenoids in recombinant microbial systems

• Katarina Kemper,
• Max Hirte,
• Markus Reinbold,
• Monika Fuchs and
• Thomas Brück

Beilstein J. Org. Chem. 2017, 13, 845–854, doi:10.3762/bjoc.13.85

• databases and computational tools [73] that enable model-based optimization such as flux-balance analyses [74]. Taking advantage of natural presence and manipulability of distinct isoprenoid pathways in both organisms (MEP in E. coli and MEV in S. cerevisiae), heterologous production of several isoprenoid

• iceberg. Potentially, modular biosynthesis that has resources to fast expanding databases will widen the amenable targets for large scale production to unforeseen extend. As a prerequisite, strain optimization of heterologous hosts has to be developing with equal progress although continuous reporting

Computational methods in drug discovery

• Sumudu P. Leelananda and
• Steffen Lindert

Beilstein J. Org. Chem. 2016, 12, 2694–2718, doi:10.3762/bjoc.12.267

• resonance (EPR) spectroscopy data has also been used in high-resolution de novo structure prediction [75][76][77]. Protein and small molecule databases Information about drug molecules and target structures is critical in using SBDD tools and many repositories collect and store such information about small

• database which has non-redundant protein sequences which are manually annotated to contain descriptions such as functional information of protein sequences and post-translational modifications [84]. PDB and Swiss-Prot are both general purpose biological databases. There are other databases that contain

• databases. One limitation of this approach can be attributed to its high complexity. When a high-resolution target structure is available, ligand growing programs such as biochemical and organic model builder (BOMB) can be used to design ligands that bind to the target without using ligand databases [155

A new paradigm for designing ring construction strategies for green organic synthesis: implications for the discovery of multicomponent reactions to build molecules containing a single ring

• John Andraos

Beilstein J. Org. Chem. 2016, 12, 2420–2442, doi:10.3762/bjoc.12.236

• ][111][112][113][114][115][116], and the creation of encoded synthesis databases that purportedly assist chemists in proposing optimum syntheses to known target molecules subject to constraints, notably number of steps, and cost and availability of commercially available starting materials [117][118

• pursued in a meaningful, targeted, and systematic fashion. However, the current structure of literature databases such as SciFinder or Reaxys do not allow for facilitated structure searches based on synthesis strategy maps. What would be needed is for a user to input a target heterocyclic structure

• This paper is dedicated to the memory of Professor Malcolm Bersohn who was a pioneer in developing computer databases to devise efficient organic syntheses at the University of Toronto.

The EIMS fragmentation mechanisms of the sesquiterpenes corvol ethers A and B, epi-cubebol and isodauc-8-en-11-ol

• Patrick Rabe and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2016, 12, 1380–1394, doi:10.3762/bjoc.12.132

• standard. Furthermore, various high quality databases containing the EI mass spectra and retention indices of thousands of compounds are available that assist in automated compound identification [2][3]. If unknown compounds are detected in natural extracts, their structure elucidation by GC–MS is more

Cyclisation mechanisms in the biosynthesis of ribosomally synthesised and post-translationally modified peptides

• Andrew W. Truman

Beilstein J. Org. Chem. 2016, 12, 1250–1268, doi:10.3762/bjoc.12.120

• annotation software, which means that some putative RiPP precursors are not even listed in databases. Furthermore, novel classes are difficult to identify precisely due to their novelty compared to known pathways. This is in contrast to terpenes, polyketide synthases or NRPSs, whose pathways are all clearly

Marine-derived myxobacteria of the suborder Nannocystineae: An underexplored source of structurally intriguing and biologically active metabolites

• Antonio Dávila-Céspedes,
• Peter Hufendiek,
• Max Crüsemann,
• Till F. Schäberle and
• Gabriele M. König

Beilstein J. Org. Chem. 2016, 12, 969–984, doi:10.3762/bjoc.12.96

• ). The genome mining results are generated by feeding the software with the INSDC code of the annotated sequences. The databases are continuously updated, thus, results presented in this part of the review may vary in ulterior analyses. Our data, however, present a useful guide for future projects. For

• = 50 nM). So far, no genome sequence is publicly available for halotolerant strains of this genus. The only sequence found in the databases belongs to the terrestrial N. exedens ATCC 25963 (see Table 1). Remarkably, this genome encodes, among a considerable number of NRPS/PKS hybrids, 10 different

Effective in silico prediction of new oxazolidinone antibiotics: force field simulations of the antibiotic–ribosome complex supervised by experiment and electronic structure methods

• Jörg Grunenberg and
• Giuseppe Licari

Beilstein J. Org. Chem. 2016, 12, 415–428, doi:10.3762/bjoc.12.45

• ) virtual screenings [28][29][30] of large molecular databases to B) sophisticated simulations of the state equations [31][32]. Nevertheless, both strategies have their own advantages and disadvantages when it comes to the reliable prediction of new drug candidates. While fast virtual screening methods

Enabling technologies and green processes in cyclodextrin chemistry

• Giancarlo Cravotto,
• Marina Caporaso,
• Laszlo Jicsinszky and
• Katia Martina

Beilstein J. Org. Chem. 2016, 12, 278–294, doi:10.3762/bjoc.12.30

• combinations has been done in two major databases [5][6]. The results were partially overlapped only in the full text searches and approximately 4000 records have been found. Further reduction of records, less than 2500, by searching in Title/Abstract/Keyword fields only resulted in more relevant publications

The Beilstein Journal of Organic Chemistry and the changing face of scientific publishing

• Martin G. Hicks and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2015, 11, 2242–2244, doi:10.3762/bjoc.11.242

• databases. In organic chemistry, laboratories are becoming digital in terms of process control, measurement and analytical techniques [2][3]. In terms of publishing, improvements would be beneficial in many areas of structure and data handling and linking. Slowly, the publishing infrastructure and workflows

• made available to experts working directly in a particular field. Further processing will allow it to be stored in structured databases for searching, and with further annotation, it can be linked or added to publications. The Protein Data Bank [15] and the Cambridge Structural Database [16] are two

• databases with inherent differences in precision and recall, as well as scientific social media [18], provide good substitutes for traditional browsing. The problems of plagiarism and self-plagiarism (also known as recycling) [19] are becoming more transparent thanks to open access and the CrossCheck system

Streptopyridines, volatile pyridine alkaloids produced by Streptomyces sp. FORM5

• Ulrike Groenhagen,
• Michael Maczka,
• Jeroen S. Dickschat and
• Stefan Schulz

Beilstein J. Org. Chem. 2014, 10, 1421–1432, doi:10.3762/bjoc.10.146

• the extract revealed that a small peak (7) eluted slightly earlier than compound 8. The mass spectrum of compound 7 matched that of 2-pentylpyridine, present in public databases [14]. From these data we concluded that the unknown compound 12 might be a 2-(pentadienyl)pyridine with conjugated side

Halogenated volatiles from the fungus Geniculosporium and the actinomycete Streptomyces chartreusis

• Tao Wang,
• Patrick Rabe,
• Christian A. Citron and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2013, 9, 2767–2777, doi:10.3762/bjoc.9.311

• . Their mass spectra pointed to the structures of a chlorodimethoxybenzene for X and a dichlorodimethoxybenzene for Y. The mass spectra of some constitutional isomers for X and Y were included in our databases and proved to be very similar, thus preventing a full structural assignment. For unambiguous

Synthesis of 5-(ethylsulfonyl)-2-methoxyaniline: An important pharmacological fragment of VEGFR2 and other inhibitors

• Miroslav Murár,
• Gabriela Addová and
• Andrej Boháč

Beilstein J. Org. Chem. 2013, 9, 173–179, doi:10.3762/bjoc.9.20

• mentioned in the patent literature [19]. No yield was given in this record. 5-(Ethylsulfonyl)-2-methoxy-1,3-dinitrobenzene (4a) is an unknown compound. No physicochemical properties or spectral data were found either in the Reaxys or in SciFinder databases. 5-(Ethylsulfonyl)-2-methoxyaniline (5), CAS [5339

• -62-8], is a compound with only limited commercial availability. For this compound no synthesis can be found in the Reaxys and SciFinder databases. There were 37 reactions in Reaxys and 191 reactions in SciFinder described. In all cases compound 5 was exclusively a starting material or reactant

The β-cyclodextrin/benzene complex and its hydrogen bonds – a theoretical study using molecular dynamics, quantum mechanics and COSMO-RS

• Jutta Erika Helga Köhler and
• Nicole Grczelschak-Mick

Beilstein J. Org. Chem. 2013, 9, 118–134, doi:10.3762/bjoc.9.15

• molecular conformers of up to 10 kcal mol−1 in the standard COSMO databases. These σ-profiles and σ-potentials were calculated with COSMOthermX for the empty β-CD models and are displayed in Figure 6 and Figure 7. Especially the σ-potentials (Figure 7) showed that the empty β-CD models were split into two