Computational toolbox for the analysis of protein–glycan interactions

• Ferran Nieto-Fabregat,
• Maria Pia Lenza,
• Angela Marseglia,
• Cristina Di Carluccio,
• Antonio Molinaro,
• Alba Silipo and
• Roberta Marchetti

Beilstein J. Org. Chem. 2024, 20, 2084–2107, doi:10.3762/bjoc.20.180

• field of computational chemistry and biochemistry: 1. AMBER [56]: AMBER (https://ambermd.org/) is the acronym for "Assisted Model Building with Energy Refinement", and it is an open-source software widely employed for molecular modelling and simulation. It is known for its stability, user-friendly

• . CHARMM [62]: CHARMM, acronym of "Chemistry at HARvard Molecular Mechanics", is a free extensively utilised molecular modelling and simulation software package. Its force field is at the core of CHARMM's capabilities, which serves as a comprehensive set of parameters and mathematical functions to describe

• design and discovery providing access to physics-based molecular modelling tools and machine learning technologies from a single modelling environment, however, it is not free-accessible. Further valuable insights into the structure and conformation of saccharides, determined by experiment and simulation

2-Heteroarylethylamines in medicinal chemistry: a review of 2-phenethylamine satellite chemical space

• Carlos Nieto,
• Alejandro Manchado,
• Ángel García-González,
• David Díez and
• Narciso M. Garrido

Beilstein J. Org. Chem. 2024, 20, 1880–1893, doi:10.3762/bjoc.20.163

• these SAR expansions is creating new chemical matter with appealing potency and selectivity profiles. The impact of the scaffold hopping exercise in these target biomarkers depends on the nature of the targets themselves. It is noteworthy, that the use of molecular modelling tools, especially molecular

The Groebke–Blackburn–Bienaymé reaction in its maturity: innovation and improvements since its 21st birthday (2019–2023)

• Cristina Martini,
• Muhammad Idham Darussalam Mardjan and
• Andrea Basso

Beilstein J. Org. Chem. 2024, 20, 1839–1879, doi:10.3762/bjoc.20.162

Spatial arrangements of cyclodextrin host–guest complexes in solution studied by ¹³C NMR and molecular modelling

• Konstantin Lebedinskiy,
• Ivan Barvík,
• Zdeněk Tošner,
• Ivana Císařová,
• Jindřich Jindřich and
• Radim Hrdina

Beilstein J. Org. Chem. 2024, 20, 331–335, doi:10.3762/bjoc.20.33

• . The 3D densities show the spatial distribution of prochiral atoms within MD simulations. Studied host–guest complexes and splitting of guests’ prochiral carbons in their 13C NMR spectra. Molecular modelling of the host–guest complexes of compound 4 with α-CD, β-CD and γ-CD. X-ray analysis of the α-CD

• 2026/5, 121 16 Praha, Czech Republic Department of Inorganic Chemistry, Faculty of Science, Charles University, Hlavova 8, 128 43 Praha, Czech Republic 10.3762/bjoc.20.33 Abstract 13C NMR spectroscopic analyses of Cs symmetric guest molecules in the cyclodextrin host cavity, combined with molecular

• modelling and solid-state X-ray analysis, provides a detailed description of the spatial arrangement of cyclodextrin host–guest complexes in solution. The chiral cavity of the cyclodextrin molecule creates an anisotropic environment for the guest molecule resulting in a splitting of its prochiral carbon

Phenanthridine–pyrene conjugates as fluorescent probes for DNA/RNA and an inactive mutant of dipeptidyl peptidase enzyme

• Josipa Matić,
• Tana Tandarić,
• Marijana Radić Stojković,
• Filip Šupljika,
• Zrinka Karačić,
• Ana Tomašić Paić,
• Lucija Horvat,
• Robert Vianello and
• Lidija-Marija Tumir

Beilstein J. Org. Chem. 2023, 19, 550–565, doi:10.3762/bjoc.19.40

• Biochemistry, Faculty of Food Technology and Biotechnology, University of Zagreb, Croatia Laboratory for Protein Biochemistry and Molecular Modelling, Division of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, Bijenička cesta 54, 10000 Zagreb, Croatia Laboratory for Molecular Plant Biology and

• Biotechnology, Division of Molecular Biology, Ruđer Bošković Institute, Bijenička cesta 54, 10000 Zagreb, Croatia 10.3762/bjoc.19.40 Abstract Two novel conjugate molecules were designed: pyrene and phenanthridine-amino acid units with a different linker length between the aromatic fragments. Molecular

• modelling combined with spectrophotometric experiments revealed that in neutral and acidic buffered water solutions conjugates predominantly exist in intramolecularly stacked conformations because of the π–π stacking interaction between pyrene and phenanthridine moieties. The investigated systems exhibited

Synthesis, α-mannosidase inhibition studies and molecular modeling of 1,4-imino-ᴅ-lyxitols and their C-5-altered N-arylalkyl derivatives

• Martin Kalník,
• Sergej Šesták,
• Juraj Kóňa,
• Maroš Bella and
• Monika Poláková

Beilstein J. Org. Chem. 2023, 19, 282–293, doi:10.3762/bjoc.19.24

• the structural moiety at C-5 (ΔElinker-E)] are also compiled. Supporting Information Supporting Information File 30: Experimental (synthesis, enzyme assay, molecular modelling). Supporting Information File 31: Copies of NMR spectra. Supporting Information File 32: Optimized QM/MM complexes

Peptide stapling by late-stage Suzuki–Miyaura cross-coupling

• Hendrik Gruß,
• Rebecca C. Feiner,
• Ridhiwan Mseya,
• David C. Schröder,
• Michał Jewgiński,
• Kristian M. Müller,
• Rafał Latajka,
• Antoine Marion and
• Norbert Sewald

Beilstein J. Org. Chem. 2022, 18, 1–12, doi:10.3762/bjoc.18.1

• hopeless to expect catching energy differences as small as that between P5.1/P5.2 by molecular modelling. Instead, we discuss qualitatively the conformational properties of the macrocycle in the two diastereomers of P5 to determine if conformers may exist with high interconversion barriers, and suggest an

• frame and is coloured according to its corresponding re-weighted relative free energy. Data is calculated on the cumulative last 500 ns of 15 accelerated molecular dynamics runs for each SMC peptide. Molecular modelling of the conformational preferences of the SMC stapled peptides P5 (with cis or trans

Structural effects of meso-halogenation on porphyrins

• Keith J. Flanagan,
• Maximilian Paradiz Dominguez,
• Zoi Melissari,
• Hans-Georg Eckhardt,
• René M. Williams,
• Dáire Gibbons,
• Caroline Prior,
• Gemma M. Locke,
• Alina Meindl,
• Aoife A. Ryan and
• Mathias O. Senge

Beilstein J. Org. Chem. 2021, 17, 1149–1170, doi:10.3762/bjoc.17.88

• present are a current limitation. To combat this, we decided to expand these series with ab-initio computational molecular modelling. We focused on the structural modelling of three series. The ground-state geometries of several members of these series were optimized at the wB97-XD/cc-pVDZ level of theory

Vicinal difluorination as a C=C surrogate: an analog of piperine with enhanced solubility, photostability, and acetylcholinesterase inhibitory activity

• Yuvixza Lizarme-Salas,
• Alexandra Daryl Ariawan,
• Ranjala Ratnayake,
• Hendrik Luesch,
• Angela Finch and
• Luke Hunter

Beilstein J. Org. Chem. 2020, 16, 2663–2670, doi:10.3762/bjoc.16.216

• compound 2, the conformational analysis of this molecule by NMR and molecular modelling studies, a comparison of the photostabilities of parent compound 1 vs derivative 2, and a comparison of the inhibitory activities of 1 vs 2 towards both AChE and BACE-1. Results and Discussion Synthesis Jacobsen and co

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

• systems more challenging. Therefore, coarse-grained models [28] for carbohydrates are generally used for molecular modelling of large systems. In terms of 3D model building, the complex topologies of glycans require dedicated molecular building procedures to convert sequence information into reliable 3D

• dynamics using molecular modelling tool like Tinker [61]. This tool is as a versatile tool for generating a 3D model for glycans. GLYCAM-web (Carbohydrate Builder). Carbohydrate builder [65] is an online tool (at http://glycam.org/) for carbohydrate structure drawing and subsequent 3D structure building

Five-component, one-pot synthesis of an electroactive rotaxane comprising a bisferrocene macrocycle

• Natalie Lagesse,
• Luca Pisciottani,
• Maxime Douarre,
• Pascale Godard,
• Brice Kauffmann,
• Vicente Martí-Centelles and
• Nathan D. McClenaghan

Beilstein J. Org. Chem. 2020, 16, 1564–1571, doi:10.3762/bjoc.16.128

• macrocycle was present, as judged by proton resonances in the 1H NMR spectrum, which along with the reaction mixture turning dark brown and the presence of a black precipitate suggested degradation. In order to evaluate the templating effect of the N,N’-dihexyl-1,4-butanediamide (3), molecular modelling

• = 0.0450, Rsigma = 0.0402) which were used in all calculations. The final R1 was 0.0454 (I > 2σ(I)) and wR2 was 0.1180 (all data). CCDC Deposition Number 1968472. Molecular modelling Monte Carlo conformational searches with the MMFF force field were carried out with the Spartan ‘18 software [30]. For each

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

• stirred at 70 °C until disappearance of the starting material as monitored by TLC. Then, the mixture was filtered on Celite and concentrated under reduced pressure. The crude product was purified by flash chromatography using the indicated solvent mixture as eluent. Molecular modelling. Calculations were

• inertia analysis was carried out by calculation of the lowest energy conformation of compounds 3–39 and block buster drugs. The conformation calculation was performed using the built-in AMMP molecular mechanics algorithm with default parameters of the VEGA ZZ molecular modelling software package v.3.0.1

Photoreversible stretching of a BAPTA chelator marshalling Ca²⁺-binding in aqueous media

• Aurélien Ducrot,
• Arnaud Tron,
• Robin Bofinger,
• Ingrid Sanz Beguer,
• Jean-Luc Pozzo and
• Nathan D. McClenaghan

Beilstein J. Org. Chem. 2019, 15, 2801–2811, doi:10.3762/bjoc.15.273

• affinity. Herein we describe the synthesis of 1, its photoswitching, and affinity changes between both forms in pseudo-physiological conditions, further rationalized by energy-minimized molecular modelling structures. Results and Discussion The synthetic pathway for the preparation of molecule 1 is shown

• the absorption at a certain wavelength. The x-intercept gives the log Kd. Molecular modelling: The molecular structure of 1E·Ca2+ and 1Z·Ca2+ were built with AMPAC 10.1. A geometry optimization was performed by energy minimization using the PM6 method; solvation was not considered. Synthetic

• . Azobenzene-BAPTA 1E and 1Z (a, b, c, d and e denote specific protons), showing idealized Ca2+ uptake and release. Counter ions omitted for clarity. Energy-minimized molecular modelling structures of 1E•Ca2+ and 1Z•Ca2+ (PM6). Electronic absorption spectra showing changes associated with photoisomerization of

1,2,3-Triazolium macrocycles in supramolecular chemistry

• Mastaneh Safarnejad Shad,
• Pulikkal Veettil Santhini and
• Wim Dehaen

Beilstein J. Org. Chem. 2019, 15, 2142–2155, doi:10.3762/bjoc.15.211

• affinity by receptor 9 was towards sulfate dianion (Ka = >104 M−1) out of all the tested anions found the trend was I− > Br− > Cl− > F− > OAc− with the dissociation constants of 4.6 × 102, 3.9 × 102, 2.3 × 102, 2.3 × 102 and 1.5 × 102 M−1, respectively. By carrying out extensive molecular modelling

2,3-Dibutoxynaphthalene-based tetralactam macrocycles for recognizing precious metal chloride complexes

• Li-Li Wang,
• Yi-Kuan Tu,
• Huan Yao and
• Wei Jiang

Beilstein J. Org. Chem. 2019, 15, 1460–1467, doi:10.3762/bjoc.15.146

• between the amide NH protons and the pyridine nitrogen atoms in 2, which pre-organizes the cavity for molecular recognition. How would this affect the binding affinity of 2? To answer this question, molecular modelling was performed. Only conformer I of 1 was used for the molecular modelling but both

Bambusuril analogs based on alternating glycoluril and xylylene units

• Tomáš Lízal and
• Vladimír Šindelář

Beilstein J. Org. Chem. 2019, 15, 1268–1274, doi:10.3762/bjoc.15.124

• characterized in the same manner as 1a. The molecular modelling showed that 1b also exists in two forms of conformers 1b-1, 1b-2 differing by the position of the glycoluril units (Figure 2). The NMR spectra (Supporting Information File 1, Figure S9) measured at low temperature featured two sets of signals

• the orientation of one glycoluril unit were obtained. The building blocks within the macrocycles connected via methylene bridges are flexible giving rise to two preferred conformers for each diastereomer. These conformers were identified by molecular modelling and also by low-temperature NMR

Precious metal-free molecular machines for solar thermal energy storage

• Meglena I. Kandinska,
• Snejana M. Kitova,
• Vladimira S. Videva,
• Stanimir S. Stoyanov,
• Stanislava B. Yordanova,
• Stanislav B. Baluschev,
• Silvia E. Angelova and
• Aleksey A. Vasilev

Beilstein J. Org. Chem. 2019, 15, 1096–1106, doi:10.3762/bjoc.15.106

• density functional theory (DFT) calculations at the B3LYP/6-31+G(d,p) level. The first step in the molecular modelling investigation was the optimization of the molecular structures of the cis and trans isomers of dyes 4a–d (with the –(CH2)nSO3− (n = 3, 4) tails oriented to be in proximity to the aza-15

Stereo- and regioselective hydroboration of 1-exo-methylene pyranoses: discovery of aryltriazolylmethyl C-galactopyranosides as selective galectin-1 inhibitors

• Alexander Dahlqvist,
• Axel Furevi,
• Niklas Warlin,
• Hakon Leffler and
• Ulf J. Nilsson

Beilstein J. Org. Chem. 2019, 15, 1046–1060, doi:10.3762/bjoc.15.102

• reported to enhance affinity for galectin-1 [34] failed in our hands, why other additional substituents to combine with the 4-fluorophenyltriazolylmethyl moiety of compound 1b remain to be discovered. Molecular modelling In order to gain understanding of the affinity-enhancing effects of the aryltriazolyl

Azologization of serotonin 5-HT₃ receptor antagonists

• Karin Rustler,
• Galyna Maleeva,
• Piotr Bregestovski and
• Burkhard König

Beilstein J. Org. Chem. 2019, 15, 780–788, doi:10.3762/bjoc.15.74

• photochromic properties were synthesized but lost antagonistic activity probably due to their increased steric demand. In ongoing studies, detailed molecular modelling is used to design potential photochromic antagonists fitting the requirements of the receptor’s binding pocket. Regarding the analysis method

Synthesis and photophysical studies of a multivalent photoreactive Ru^II-calix[4]arene complex bearing RGD-containing cyclopentapeptides

• Sofia Kajouj,
• Lionel Marcelis,
• Alice Mattiuzzi,
• Adrien Grassin,
• Damien Dufour,
• Pierre Van Antwerpen,
• Didier Boturyn,
• Eric Defrancq,
• Mathieu Surin,
• Julien De Winter,
• Pascal Gerbaux,
• Ivan Jabin and
• Cécile Moucheron

Beilstein J. Org. Chem. 2018, 14, 1758–1768, doi:10.3762/bjoc.14.150

• autocorrelation function were employed to judge the quality of the fits. For molecular modelling simulations, the initial structure of the ruthenium complex was obtained from previous DFT calculations using a previously reported methodology [82]. The geometries of the RAFTs and calixarene were built using DS

• BIOVIA© software and geometry-optimized using the CHARMM force-field, taking into account previous molecular modelling simulations on cyclic peptides [83]. The structures were linked together yielding through several steps of energy minimizations, maintaining the ruthenium complex constrained in

Phosphoramidite building blocks with protected nitroxides for the synthesis of spin-labeled DNA and RNA

• Timo Weinrich,
• Eva A. Jaumann,
• Ute M. Scheffer,
• Thomas F. Prisner and
• Michael W. Göbel

Beilstein J. Org. Chem. 2018, 14, 1563–1569, doi:10.3762/bjoc.14.133

• , 22 h; (e) N,N-diisopropylamino(2-cyanoethyl)phosphoramidic chloride, Et3N, CH2Cl2, rt, 23 h. Spin–spin distances in oligonucleotides 22c–27c determined by PELDOR and by molecular modelling. The predicted distance is an average of N–N, N–O, O–N, and O–O distances. Supporting Information Supporting

A three-armed cryptand with triazine and pyridine units: synthesis, structure and complexation with polycyclic aromatic compounds

• Claudia Lar,
• Adrian Woiczechowski-Pop,
• Attila Bende,
• Ioana Georgeta Grosu,
• Natalia Miklášová,
• Elena Bogdan,
• Niculina Daniela Hădade,
• Anamaria Terec and
• Ion Grosu

Beilstein J. Org. Chem. 2018, 14, 1370–1377, doi:10.3762/bjoc.14.115

• , Slovakia 10.3762/bjoc.14.115 Abstract The aromatic nucleophilic substitution reaction based synthesis of a three-armed cryptand displaying 2,4,6-triphenyl-1,3,5-triazine units as caps and pyridine rings in the bridges, along with NMR, MS and molecular modelling-based structural analysis of this compound

• are reported. Appropriate NMR and molecular modelling investigations proved the formation of 1:1 host–guest assemblies between the investigated cryptand and some polynuclear aromatic hydrocarbons or their derivatives. Keywords: aromatic guests; aromatic nucleophilic substitution; cryptand; NMR

• pyrene, anthracene and 1,5-dihydroxynaphthalene as guest molecules was investigated by NMR titration experiments and molecular modelling. The spectra recorded during the NMR titrations of cryptand 2 with increasing amounts of the named guests (ratio 1:9 to 9:1), revealed only one set of signals. However

Synthetic mRNA capping

• Fabian Muttach,
• Nils Muthmann and
• Andrea Rentmeister

Beilstein J. Org. Chem. 2017, 13, 2819–2832, doi:10.3762/bjoc.13.274

• compared to the standard cap. The cap analogue is exclusively incorporated in the correct (forward) orientation and molecular modelling studies pointed to a stronger binding of the propargyl-modified cap to eIF4E compared to the standard cap [65]. With regard to translational activity, several dinucleotide

Enzymatic synthesis of glycosides: from natural O- and N-glycosides to rare C- and S-glycosides

• Jihen Ati,
• Pierre Lafite and
• Richard Daniellou

Beilstein J. Org. Chem. 2017, 13, 1857–1865, doi:10.3762/bjoc.13.180

• the fast screening of their activities, as well as powerful molecular modelling and crystallization of proteins. No doubt then that such biocatalysts will represent a competitive tool for glycosylation so to obtain complex O-, S- or C-glycoconjugates of biological interests. Mechanisms of O-GTs

Glycoscience@Synchrotron: Synchrotron radiation applied to structural glycoscience

• Serge Pérez and
• Daniele de Sanctis

Beilstein J. Org. Chem. 2017, 13, 1145–1167, doi:10.3762/bjoc.13.114

• interaction with the protein led to the development of different molecular modelling methods. A somehow indirect application of the fine specificity of the binding of oligosaccharides to lectins has been elegantly developed to solve the phase problem in protein crystallography. Selenium-labelled carbohydrates

• domains of the two allomorphs of starch granules found in cereal and tubers had been established from a series of experimental observations (X-ray and electron crystallography) and molecular modelling. While displaying differences in their mode of interactions, both allomorphs are characterized by a