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

Progress and challenges in the synthesis of sequence controlled polysaccharides

• Giulio Fittolani,
• Theodore Tyrikos-Ergas,
• Denisa Vargová,
• Manishkumar A. Chaube and
• Martina Delbianco

Beilstein J. Org. Chem. 2021, 17, 1981–2025, doi:10.3762/bjoc.17.129

• ]. The replacement of a single Glc unit with a Man unit was sufficient to disrupt this secondary structure and significantly increased the isolated yield of the final compounds. Molecular dynamic (MD) simulations predicted a compact helical conformation for the fully deprotected compound, confirmed by

• ][260]. The automated solid-phase approach required only two BBs with the amino group protected either with the N-TCA 79 or with the N-Cbz group 80 (Scheme 12). Compounds 81–85 served as standards to explore the conformational space of COS with different PA. NMR analysis and MD simulations revealed the

Double-headed nucleosides: Synthesis and applications

• Vineet Verma,
• Jyotirmoy Maity,
• Vipin K. Maikhuri,
• Ritika Sharma,
• Himal K. Ganguly and
• Ashok K. Prasad

Beilstein J. Org. Chem. 2021, 17, 1392–1439, doi:10.3762/bjoc.17.98

• that resulted in the formation of two novel nucleic acid motifs. The novel nucleic acid motifs could be incorporated either single or multiple times in dsDNA duplexes without altering its stability. It was revealed by molecular dynamics (MD) simulations that the DNA sugar–phosphate backbone

• strands. Oligonucleotides with fourteen consecutive incorporations of different double-headed nucleosides were synthesized and the DNA duplexes showed increased stability owing to increased stacking interactions among the nucleobases of the opposite strands [72]. Molecular dynamics simulations

• simulations [15][22]. The double-headed nucleoside 157a was further used for the synthesis of 5-(phenyltriazol)-2′-deoxyuridine-modified 2′-O-methyl mixmer antisense oligonucleotides (AOs). The obtained AOs were investigated for their potential to induce exon skipping in DMD (Duchenne muscular dystrophy

Kinetics of enzyme-catalysed desymmetrisation of prochiral substrates: product enantiomeric excess is not always constant

• Peter J. Halling

Beilstein J. Org. Chem. 2021, 17, 873–884, doi:10.3762/bjoc.17.73

• defined in such a way that they were expected to be usually of the order of magnitude of 1, so assigning values for kinetic simulations was easier. One type of grouping of rate constants was found to come up regularly in the analytical solution of equations resulting from the quasi-steady state

• ping-pong, second, 1 and 2 for ping-pong, first). For the ping-pong, both mechanism, there are two sets of SC values, SCRf etc. for steps 1 and 2, and SCR2f etc. for steps 3 and 4. These pseudo-specificity constants have units of M−1 s−1, so were not used directly as input parameters to simulations

• of other enzyme parameters, simulations were routinely run for an E value of 39 (initial product ee 0.95), which makes changes clearer to display. A number of other enzyme parameters were found to have negligible effects on the product ee at 95% equilibrium conversion: KMD, k−2R/k−1, E · k−2S/k−1. As

Direct synthesis of anomeric tetrazolyl iminosugars from sugar-derived lactams

• Michał M. Więcław and
• Bartłomiej Furman

Beilstein J. Org. Chem. 2021, 17, 115–123, doi:10.3762/bjoc.17.12

• , we were not able to fit any of these simulations to the experimental data with sufficient certainty. For the inquisitive readers, this work is fully described in Supporting Information File 1. Mechanism of the reaction As mentioned previously, we observed Ugi–azide products, despite the absence of a

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

• perfect geometry to form the capsid irreversibly [80]. However, this approach is too simplistic and does not take into consideration kinetic traps where capsid formation cannot be completed due to a lack of assembly units. As a result, the use of assembly simulations and mathematical calculations shows

Water-soluble host–guest complexes between fullerenes and a sugar-functionalized tribenzotriquinacene assembling to microspheres

• Si-Yuan Liu,
• Xin-Rui Wang,
• Man-Ping Li,
• Wen-Rong Xu and
• Dietmar Kuck

Beilstein J. Org. Chem. 2020, 16, 2551–2561, doi:10.3762/bjoc.16.207

• hydrophobic effect and to host–guest π–π interactions. Hydrophobic surface simulations showed that TBTQ-(OG)6 and C60 forms an amphiphilic supramolecular host–guest complex, which further assembles to microspheres with diameters of 0.3–3.5 μm, as determined by scanning electron microscopy. Keywords

• the slight shift of the peaks further indicates the successful complexation of TBTQ-(OG)6 and C60. Simulations of complex TBTQ-(OG)6 C60 in water. In spite of numerous attempts, we failed to obtain good-quality crystals to determine the binding conformation of complex TBTQ-(OG)6 C60 by X-ray

Comparative ligand structural analytics illustrated on variably glycosylated MUC1 antigen–antibody binding

• Christopher B. Barnett,
• Tharindu Senapathi and
• Kevin J. Naidoo

Beilstein J. Org. Chem. 2020, 16, 2540–2550, doi:10.3762/bjoc.16.206

• Africa 10.3762/bjoc.16.206 Abstract When faced with the investigation of the preferential binding of a series of ligands against a known target, the solution is not always evident from single structure analysis. An ensemble of structures generated from computer simulations is valuable; however, visual

• approach by investigating the in-silico binding of a peptide and glycopeptide epitope of the glycoprotein Mucin 1 (MUC1) binding with the antibody AR20.5. To study the binding, we performed molecular dynamics simulations using OpenMM and then used the Galaxy platform for data analysis. The same analysis

• . and others [14][16] provides a foundation for further investigation into the binding of glycopeptide antigens to antibodies using computational modeling. Molecular dynamics (MD) simulations and analysis thereof are a well-known ingredient of the in-silico process for mechanistic screening of

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

• study of these glycan-mediated interactions can provide unique insight into the molecular interplay governing these processes. In addition, it can provide structural snapshots in atomistic detail that can be used to generate molecular dynamics simulations describing a wider picture underpinning glycan

• /glycoproteomics to carbohydrate 3D model building and validation in Privateer Many fields, for example pharmaceutical design and engineering [58], molecular dynamics simulations [59] and protein interaction studies [60], rely upon structural biology to produce accurate atomistic descriptions of glycoproteins

Dawn of a new era in industrial photochemistry: the scale-up of micro- and mesostructured photoreactors

• Emine Kayahan,
• Mathias Jacobs,
• Leen Braeken,
• Leen C.J. Thomassen,
• Simon Kuhn,
• Tom van Gerven and
• M. Enis Leblebici

Beilstein J. Org. Chem. 2020, 16, 2484–2504, doi:10.3762/bjoc.16.202

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

• computational tools was inspected for general features related to sketching, representing and model building, all of which could be further used as input for translation into other formats, search from glycan databases or complex calculations such as molecular simulations. Several tools feature an interactive

• rotatable bonds. Nonetheless, recent developments in carbohydrate force fields enable to model and reproduce the energies associated with minute geometrical changes. The currently available force fields which are parameterised for carbohydrates are also capable of carrying out simulations of the

• oligosaccharides containing additional groups like sulfates, phosphates etc. [24] Generally used force fields for the Molecular Mechanics (MD) simulation of carbohydrates are CHARMM [25], GLYCAM [26], and GROMOS [27]. The structural complexity increases the computational cost, which makes simulations of large

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

• undetected because of their intrinsic structural disorder. In this work we use molecular dynamics (MD) simulations to provide insight into N-glycans’ 3D structure by analysing the effects of a set of very specific modifications found in plants and invertebrate N-glycans, which are immunogenic in humans. We

• represents an essential resource to advance glycomics [11][12][13][14][15], while molecular simulations fit in very well as complementary and orthogonal techniques to support and advance structural glycobiology research. Indeed, current high performance computing (HPC) technology allows us to study realistic

• model systems [16][17] and to reach experimental timescales [18], so that computing can now contribute as one of the leading research methods in structural glycobiology. One of the most interesting and remarkably challenging areas in glycoscience research that HPC simulations can address is the study of

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

• (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

Synthesis, docking study and biological evaluation of ᴅ-fructofuranosyl and ᴅ-tagatofuranosyl sulfones as potential inhibitors of the mycobacterial galactan synthesis targeting the galactofuranosyltransferase GlfT2

• Marek Baráth,
• Jana Jakubčinová,
• Zuzana Konyariková,
• Stanislav Kozmon,
• Katarína Mikušová and
• Maroš Bella

Beilstein J. Org. Chem. 2020, 16, 1853–1862, doi:10.3762/bjoc.16.152

• mechanism studies using computational chemistry methods. The probable reaction mechanisms were studied by hybrid DFT QM/MM molecular dynamics simulations [11] where the possible transition state (TS) structures were localized. The observation of the possible TS structure opens the opportunities for the in

• structures. All fructofuranose and tagatofuranose derivatives were docked into the GlfT2 structure obtained by QM/MM molecular dynamics simulations, which representes the structure close to the transition state structure of the GlfT2 catalytic reaction. The best ten docking poses of each docked molecule were

Models of necessity

• Timothy Clark and
• Martin G. Hicks

Beilstein J. Org. Chem. 2020, 16, 1649–1661, doi:10.3762/bjoc.16.137

• layer of imperfection. Biological systems are even more complex, with an extraordinarily large concentration of molecules in, for instance, cells. In such systems, the necessity to sample all possible geometrical configurations of the system becomes the second major hurdle to accurate simulations. Even

• intelligence. The consequence is that we must distinguish far more clearly between the chemical ontology of AI and ML and our everyday language. The use of the Lewis model goes even further. Biomolecular simulations are based on molecular force fields, which are simply Lewis structures translated into a

• -atomic representation [73]. These force fields have attained a remarkable level of accuracy for proteins, so that force-field based simulations have become predictive in many fields of biology, medicinal chemistry and biophysics [74]. Models, approximations and paradigms Despite the many advances made

Synthesis and properties of tetrathiafulvalenes bearing 6-aryl-1,4-dithiafulvenes

• Aya Yoshimura,
• Hitoshi Kimura,
• Kohei Kagawa,
• Mayuka Yoshioka,
• Toshiki Itou,
• Dhananjayan Vasu,
• Takashi Shirahata,
• Hideki Yorimitsu and
• Yohji Misaki

Beilstein J. Org. Chem. 2020, 16, 974–981, doi:10.3762/bjoc.16.86

• bearing 1,3-dithiol-2-ylidenes took place efficiently to produce the corresponding π-conjugated molecules. We also succeeded in the estimation of the oxidation potentials and number of electrons involved in each oxidation step of the obtained compounds by digital simulations. Keywords: cross-conjugated

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

• the receptor using the Surflex-Dock Geom (SFXC) protocol [41][42][43] to evaluate the binding affinity of the ligand for the HDAC8 receptor. The C-scoring method was used to calculate these binding affinities and binding scores are given in −log10(Kd) values [45]. Docking simulations where ran

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

• (δC 33.1 for 2 vs 28.3 for 1), a decisive evidence was acquired from spin system simulations using the software ‘nmrpeak’ [19], which gave the best match to the experimentally obtained 1H NMR spectrum with the setting of 3JH8,H9 = 15.6 Hz and 3JH7,H8 = 9.5 Hz (Figure 3). Thus, the C8 geometry was

• system simulations were performed using the freeware nmrpeak.exe [19]. Antimicrobial assay Antimicrobial assays were carried out in a similar manner as described in [18]. The antimicrobial activity was evaluated by the liquid microculture method using round-bottomed 96-well microtiter plates against five

Unexpected one-pot formation of the 1H-6a,8a-epiminotricyclopenta[a,c,e][8]annulene system from cyclopentanone, ammonia and dimethyl fumarate. Synthesis of highly strained polycyclic nitroxide and EPR study

• Sergey A. Dobrynin,
• Igor A. Kirilyuk,
• Yuri V. Gatilov,
• Andrey A. Kuzhelev,
• Olesya A. Krumkacheva,
• Matvey V. Fedin,
• Michael K. Bowman and
• Elena G. Bagryanskaya

Beilstein J. Org. Chem. 2019, 15, 2664–2670, doi:10.3762/bjoc.15.259

• molecules along the a-axis. EPR measurements Figure 4 demonstrates the X-band CW EPR spectra of nitroxide 6 in water/glycerol solution at 180 K and at room temperature with simulations (red) using the parameters listed in the caption. The electron spin relaxation of nitroxides with different bulky

• experimental spectra and the red lines are simulations for hfi, g-factor and correlation times of A(N) = [0.71; 0.71; 3.71] mT, g = [2.0087; 2.0055; 2.0019], tcorr = 0.53 ns (at 298 K). Synthesis of compound 1. Possible mechanism for the formation of 1. Synthesis of nitroxide 6. A proposed mechanism for

Current understanding and biotechnological application of the bacterial diterpene synthase CotB2

• Ronja Driller,
• Daniel Garbe,
• Norbert Mehlmer,
• Monika Fuchs,
• Keren Raz,
• Dan Thomas Major,
• Thomas Brück and
• Bernhard Loll

Beilstein J. Org. Chem. 2019, 15, 2355–2368, doi:10.3762/bjoc.15.228

• date, CotB2 represents the best studied bacterial diterpene synthase. Its reaction mechanism has been addressed by isoptope labeling, targeted mutagenesis and theoretical computations in the gas phase, as well as full enzyme molecular dynamic simulations. By X-ray crystallography different snapshots of

• ], density functional theory calculations [33] as well as QM/MM simulations [37]. Variants of CotB2 open the route to a novel product portfolio with altered cyclic carbon skeletons, which can be converted into bioactive compounds by chemo-enzymatic methodologies. Modification descriptions are composed

α-Photooxygenation of chiral aldehydes with singlet oxygen

• Dominika J. Walaszek,
• Magdalena Jawiczuk,
• Jakub Durka,
• Olga Drapała and
• Dorota Gryko

Beilstein J. Org. Chem. 2019, 15, 2076–2084, doi:10.3762/bjoc.15.205

• force field within 5 kcal/mol energy ranges. Further optimization was carried out at DFT level using the B3LYP functional and the Def2TZVP basis set in the Gaussian 09 [36]. Simulations of ECD spectra were carried out with TD-DFT methods for conformers found in the range of 2.5 kcal/mol. The B3LYP

Archangelolide: A sesquiterpene lactone with immunobiological potential from Laserpitium archangelica

• Silvie Rimpelová,
• Michal Jurášek,
• Lucie Peterková,
• Jiří Bejček,
• Vojtěch Spiwok,
• Miloš Majdl,
• Michal Jirásko,
• Miloš Buděšínský,
• Juraj Harmatha,
• Eva Kmoníčková,
• Pavel Drašar and
• Tomáš Ruml

Beilstein J. Org. Chem. 2019, 15, 1933–1944, doi:10.3762/bjoc.15.189

• ). The first round of simulations (1–10 ns) of compound 1 docking into SERCA cavity with compound 1 constrained as described (simulation 1) showed the presence of hydrophobic interactions of ligand side chains with Phe256, Val263, Ile829 and the hydrophobic part of Gln259 amino acid residues. Gln259 was

• the main residue involved in hydrophilic interaction. Interestingly, during the simulations in water environment, compound 1 had the tendency to escape from the SERCA cavity. In simulation 2 of compound 1 rotated by 180° with constrained positions (10 ns), interactions with Phe256 and hydrophobic

• and Figure 5). During simulations with SERCA positioned in a phospholipid membrane (simulation 4; 1 ns), the free space between individual phospholipids in the cell membrane was filled. SERCA remained stable and tightly embedded in the membrane and did not show any tendency to escape from it. Compound

Functional panchromatic BODIPY dyes with near-infrared absorption: design, synthesis, characterization and use in dye-sensitized solar cells

• Quentin Huaulmé,
• Cyril Aumaitre,
• Outi Vilhelmiina Kontkanen,
• David Beljonne,
• Alexandra Sutter,
• Gilles Ulrich,
• Renaud Demadrille and
• Nicolas Leclerc

Beilstein J. Org. Chem. 2019, 15, 1758–1768, doi:10.3762/bjoc.15.169

• also a reduced energy driving force for charge separation at the TiO2 surface. To check this hypothesis, we performed TD-DFT simulations of the optical absorption spectra of the 4 representative dyes. The results reported in Figure 3 are fully consistent with the predictions from the one-electron

Water inside β-cyclodextrin cavity: amount, stability and mechanism of binding

• Stiliyana Pereva,
• Valya Nikolova,
• Silvia Angelova,
• Tony Spassov and
• Todor Dudev

Beilstein J. Org. Chem. 2019, 15, 1592–1600, doi:10.3762/bjoc.15.163

• disordered and mobile, and that the OH groups of the host β-CD may rotate [17]. Studies with molecular dynamics simulations have found only four water molecules inside the host β-CD cavity [18]. The energetics of the CD hydration/dehydration have been investigated as well. Experimental studies have been able

Synthesis and conformational preferences of short analogues of antifreeze glycopeptides (AFGP)

• Małgorzata Urbańczyk,
• Michał Jewgiński,
• Joanna Krzciuk-Gula,
• Jerzy Góra,
• Rafał Latajka and
• Norbert Sewald

Beilstein J. Org. Chem. 2019, 15, 1581–1591, doi:10.3762/bjoc.15.162

• into the ice lattice [12], others investigated the adsorption process on different surfaces via atomic force microscopy [10][13][14]. The antifreeze activity has been correlated with long-range perturbation of hydration dynamics [15]. Latest molecular dynamics simulations suggest that AFGP reversibly