Peptide–polymer ligands for a tandem WW-domain, an adaptive multivalent protein–protein interaction: lessons on the thermodynamic fitness of flexible ligands

• Katharina Koschek,
• Vedat Durmaz,
• Oxana Krylova,
• Marek Wieczorek,
• Shilpi Gupta,
• Martin Richter,
• Alexander Bujotzek,
• Christina Fischer,
• Rainer Haag,
• Christian Freund,
• Marcus Weber and
• Jörg Rademann

Beilstein J. Org. Chem. 2015, 11, 837–847, doi:10.3762/bjoc.11.93

• Informationstechnik Berlin, Numerical Analysis and Modelling, Takustr. 7, 14195 Berlin, Germany 10.3762/bjoc.11.93 Abstract Three polymers, poly(N-(2-hydroxypropyl)methacrylamide) (pHPMA), hyperbranched polyglycerol (hPG), and dextran were investigated as carriers for multivalent ligands targeting the adaptive

Orthogonal dual-modification of proteins for the engineering of multivalent protein scaffolds

• Michaela Mühlberg,
• Michael G. Hoesl,
• Christian Kuehne,
• Jens Dernedde,
• Nediljko Budisa and
• Christian P. R. Hackenberger

Beilstein J. Org. Chem. 2015, 11, 784–791, doi:10.3762/bjoc.11.88

• scaffolds as well as NCAAs to provide multiple distinct probes for the generation of individually designed protein binders. An important parameter in the future will be the combination with protein modelling as well as the implementation of different linker lengths between the protein and the binding units

Inclusion of trans-resveratrol in methylated cyclodextrins: synthesis and solid-state structures

• Lee Trollope,
• Dyanne L. Cruickshank,
• Terence Noonan,
• Susan A. Bourne,
• Milena Sorrenti,
• Laura Catenacci and
• Mino R. Caira

Beilstein J. Org. Chem. 2014, 10, 3136–3151, doi:10.3762/bjoc.10.331

• is worth consideration in molecular modelling studies that address CD-RSV interaction in that medium. Equally significant in the context of molecular modelling is our observation in the solid-state of the potentially more probable bridging role of water in mediating host–guest binding, this feature

Come-back of phenanthridine and phenanthridinium derivatives in the 21st century

• Lidija-Marija Tumir,
• Marijana Radić Stojković and
• Ivo Piantanida

Beilstein J. Org. Chem. 2014, 10, 2930–2954, doi:10.3762/bjoc.10.312

• instance, adenine derivative 15 (Figure 6) selectively recognized the complementary nucleotide (UMP) by specific change in the UV–vis spectrum of phenanthridine subunits and high affinity [75]. Molecular modelling studies proposed a structure of the 15–UMP complex stabilized by a set of intra- and

• analogue, dihydroimidazophenanthridinium cation characterised by cyclic structure connecting positions 5 and 6, showed promising antiproliferative activity [3][98][99]. Molecular modelling results and some preliminary experiments suggest intercalative binding mode, however up till now interactions with

Self-assembled monolayers of shape-persistent macrocycles on graphite: interior design and conformational polymorphism

• Joscha Vollmeyer,
• Friederike Eberhagen,
• Sigurd Höger and
• Stefan-S. Jester

Beilstein J. Org. Chem. 2014, 10, 2774–2782, doi:10.3762/bjoc.10.294

• models. Backbone geometries of the shape-persistent macrocycles with different interiors were derived by force-field modelling (Spartan ‘08) restricted to 2D (including interaction with a graphene layer with fixed atom positions), and extraannular octadecyloxy side chains in staggered (anti) conformation

Towards the sequence-specific multivalent molecular recognition of cyclodextrin oligomers

• Michael Kurlemann and
• Bart Jan Ravoo

Beilstein J. Org. Chem. 2014, 10, 2428–2440, doi:10.3762/bjoc.10.253

• is one order of magnitude higher than the comparable monovalent binding constants of α-CD/17 and α-CD/18. This is caused by the symmetry effect, which is even higher due to the negligence of different molecular recognition motifs for the simplified modelling. The thermodynamic parameters surprisingly

• the simplified multivalent binding model can be used for modelling the ITC data, resulting in an EM of 0.12 mM. Thus, the system 7/13 shows positive chelate cooperativity as well (Ki·EM ≈ 5) and double-stranded structures are preferentially formed. All in all, the guest strand 13 shows preferred

Supercritical carbon dioxide: a solvent like no other

• Jocelyn Peach and
• Julian Eastoe

Beilstein J. Org. Chem. 2014, 10, 1878–1895, doi:10.3762/bjoc.10.196

• . have a large body of both practical and theoretical work around polymer solubility in carbon dioxide [84]. The first reported use of ab initio modelling to design oxygenated hydrocarbon polymers for use in CO2 was in 2009, where one oligomer and two polymers were synthesised and found to be soluble in

• CO2 after ab initio predictions. The molecules OAO, PVMME and PVMEE were derived from the smaller CO2-philic moieties MIA, 2MME and 2MEE. It is hoped that other macromolecules could also be designed based on these moieties in time (Figure 4). Unfortunately, ab initio modelling can be quite limiting as

Photoswitchable precision glycooligomers and their lectin binding

• Daniela Ponader,
• Sinaida Igde,
• Marko Wehle,
• Katharina Märker,
• Mark Santer,
• David Bléger and
• Laura Hartmann

Beilstein J. Org. Chem. 2014, 10, 1603–1612, doi:10.3762/bjoc.10.166

• modelling for ligand binding. Ongoing studies further investigate ligand binding by additional techniques such as isothermal titration calorimetry and fluorescence spectroscopy. Overall, we have successfully developed photoswitchable glycomimetics that allow for a stimulus-induced change in binding affinity

Rational design of cyclopropane-based chiral PHOX ligands for intermolecular asymmetric Heck reaction

• Marina Rubina,
• William M. Sherrill,
• Alexey Yu. Barkov and
• Michael Rubin

Beilstein J. Org. Chem. 2014, 10, 1536–1548, doi:10.3762/bjoc.10.158

• Abstract A novel class of chiral phosphanyl-oxazoline (PHOX) ligands with a conformationally rigid cyclopropyl backbone was synthesized and tested in the intermolecular asymmetric Heck reaction. Mechanistic modelling and crystallographic studies were used to predict the optimal ligand structure and helped

Aza-Diels–Alder reaction between N-aryl-1-oxo-1H-isoindolium ions and tert-enamides: Steric effects on reaction outcome

• Amitabh Jha,
• Ting-Yi Chou,
• Zainab ALJaroudi,
• Bobby D. Ellis and
• T. Stanley Cameron

Beilstein J. Org. Chem. 2014, 10, 848–857, doi:10.3762/bjoc.10.81

• formation of 2-(2-substitued-aryl)-3-(2-(2-oxopyrrolidin-1-yl)vinyl)isoindolin-1-one analogues indicating steric hinderance as the cause of deviation. The probable mechanism of the reaction based on the results from X-ray crystallography and molecular modelling is discussed. Keywords: alkene addition

• -phenyl)-1-oxo-1H-isoindolium ions by molecular modelling. Like biphenyl, the N-phenyl-1-oxo-1H-isoindolium ions were expected to show extended conjugation and not to acquire a mutually perpendicular conformation with respect to the N-phenyl and the oxoisoindolium moieties. Like biphenyl [44], the

Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics

• Gijs Koopmanschap,
• Eelco Ruijter and
• Romano V.A. Orru

Beilstein J. Org. Chem. 2014, 10, 544–598, doi:10.3762/bjoc.10.50

Novel supramolecular affinity materials based on (−)-isosteviol as molecular templates

• Christina Lohoelter,
• Malte Brutschy,
• Daniel Lubczyk and
• Siegfried R. Waldvogel

Beilstein J. Org. Chem. 2013, 9, 2821–2833, doi:10.3762/bjoc.9.317

• additional base and operation in a sealed tube provided a satisfactory yield of 8 (Scheme 3) [61]. By molecular modelling the structural features can be visualized (Figure 5). A relatively closed C3-symmetric cleft is formed by all-syn-8 (Figure 5a), whereas the less symmetric anti,anti,syn-8 (Figure 5b

• . Furthermore, a new set of signals (Figure 7, green) can be seen in the product spectrum which show typical shifts of 1,2-disubstituted alkenes. Since the obtained analytical data strongly indicate the existence of cage compound 19, molecular modelling calculations (Figure 8, MacroModel 9.3.5) indicate a

• compounds, see Supporting Information File 1. Unique structural features of (−)-isosteviol. Triphenylene ketal based on (−)-isosteviol. Structural features of triptycene derivatives. Hexaammoniumtriptycene hexachloride 4 and 15-oxo-derivatives 5a–c of (–)-isosteviol. Molecular modelling structures (Spartan

Space filling of β-cyclodextrin and β-cyclodextrin derivatives by volatile hydrophobic guests

• Sophie Fourmentin,
• Anca Ciobanu,
• David Landy and
• Gerhard Wenz

Beilstein J. Org. Chem. 2013, 9, 1185–1191, doi:10.3762/bjoc.9.133

• Saarbrücken, Germany 10.3762/bjoc.9.133 Abstract The inclusion of volatile derivatives of benzene and cyclohexane in β-cyclodextrin (β-CD), hydroxypropyl-β-CD, and hydrophilic β-CD-thioethers was investigated by static headspace gas chromatography (HS-GC) and molecular modelling. The obtained binding

• constants strongly increase with the amount of space filling of the CD cavity and the salt concentration. β-CD thioethers show a 3–10 times higher binding potential than native β-CD. Keywords: cyclodextrins; inclusion compound; molecular modelling; space filling; static headspace gas chromatography; vapor

• for benzene derivatives and 7, 10, 12 and 15 mL for cyclohexane derivatives, respectively). Molecular modelling Simulations of inclusion compounds for each benzene derivative into the cavity of host 4 were realized by means of Macromodel [45] with MMFF force field and GB/SA simulation of water [46

Enhancement of efficiency in organic photovoltaic devices containing self-complementary hydrogen-bonding domains

• Rohan J. Kumar,
• Jegadesan Subbiah and
• Andrew B. Holmes

Beilstein J. Org. Chem. 2013, 9, 1102–1110, doi:10.3762/bjoc.9.122

• -bonding interactions and insufficient to explain the changes in chemical shift at the concentrations observed here. However, given the strongly dipolar nature of the compound, the role of dipole-based interactions cannot be ruled out. We then turned to molecular modelling to shed further light on the

Development of peptidomimetic ligands of Pro-Leu-Gly-NH₂ as allosteric modulators of the dopamine D₂ receptor

• Swapna Bhagwanth,
• Ram K. Mishra and
• Rodney L. Johnson

Beilstein J. Org. Chem. 2013, 9, 204–214, doi:10.3762/bjoc.9.24

• chirality at the C-8’a bridgehead carbon atom. This difference, it was postulated, has an effect on the conformation adopted by the thiazolidine ring within the spiro-bicyclic scaffold. In particular, modelling studies suggested that the pucker of the thiazolidine ring in negative modulators 29b and 49b

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

• large industrial processes [24][25][26]. Our intention for this study was to find a “modular, robust molecular-modelling workflow” for how to analyse the formation of cyclodextrin complexes for many guest molecules in general, before extensive experimental work is carried out. Lemon grass oil [27] or

Inclusion of the insecticide fenitrothion in dimethylated-β-cyclodextrin: unusual guest disorder in the solid state and efficient retardation of the hydrolysis rate of the complexed guest in alkaline solution

• Dyanne L. Cruickshank,
• Natalia M. Rougier,
• Raquel V. Vico,
• Susan A. Bourne,
• Elba I. Buján,
• Mino R. Caira and
• Rita H. de Rossi

Beilstein J. Org. Chem. 2013, 9, 106–117, doi:10.3762/bjoc.9.14

• . There was an abnormally large peak situated close to the phenyl ring but it was not in the plane of the phenyl group. Two additional hexagonal rings were discerned in the difference Fourier map, suggesting two other guest-molecule positions. After many attempts at modelling the disorder, three

Thioester derivatives of the natural product psammaplin A as potent histone deacetylase inhibitors

• Matthias G. J. Baud,
• Thomas Leiser,
• Vanessa Petrucci,
• Mekala Gunaratnam,
• Stephen Neidle,
• Franz-Josef Meyer-Almes and
• Matthew J. Fuchter

Beilstein J. Org. Chem. 2013, 9, 81–88, doi:10.3762/bjoc.9.11

• heterocyclic N-thioethylamide-based HDAC inhibitors based on the psammaplin A pharmacophore and rationalised the results using computational modelling [22]. While prereduced psammaplin A and thiol-containing analogues displayed nanomolar to subnanomolar potencies in vitro, they only displayed modest potencies

Peptides presenting the binding site of human CD4 for the HIV-1 envelope glycoprotein gp120

• Julia Meier,
• Kristin Kassler,
• Heinrich Sticht and
• Jutta Eichler

Beilstein J. Org. Chem. 2012, 8, 1858–1866, doi:10.3762/bjoc.8.214

• above. Absorbances (A) were read at 492 nm, and corrected for the respective blanks (wells without X5). All binding assays were performed at least twice, each time in duplicate. MD simulation Computational analysis included modelling of peptide–gp120 complexes followed by molecular dynamics simulation

Regioselective synthesis of 7,8-dihydroimidazo[5,1-c][1,2,4]triazine-3,6(2H,4H)-dione derivatives: A new drug-like heterocyclic scaffold

• Nikolay T. Tzvetkov,
• Harald Euler and
• Christa E. Müller

Beilstein J. Org. Chem. 2012, 8, 1584–1593, doi:10.3762/bjoc.8.181

• (HSQC and HMBC) in combination with 1H and 13C NMR, and additionally by LC/ESI-MS (m/z 287 [M + H]+/285 [M − H]− for 24, 355 [M + H]+/353 [M − H]− for 25). Molecular modelling was performed to calculate the respective geometries by using the MMFF95 force field [27] assuming an N1–C5 ring fusion during

A macrolactonization approach to the total synthesis of the antimicrobial cyclic depsipeptide LI-F04a and diastereoisomeric analogues

• James R. Cochrane,
• Dong Hee Yoon,
• Christopher S. P. McErlean and
• Katrina A. Jolliffe

Beilstein J. Org. Chem. 2012, 8, 1344–1351, doi:10.3762/bjoc.8.154

• hydrogen bonds (Figure 2). The temperature dependence of the chemical shifts of the signals attributable to the amide NHs of 1 in d6-DMSO was determined experimentally and confirmed the involvement of the D-Ala and D-Asn amide protons in hydrogen bonds [31] as suggested by the modelling studies of the

Formation of smectic phases in binary liquid crystal mixtures with a huge length ratio

• Nadia Kapernaum,
• Friederike Knecht,
• C. Scott Hartley,
• Jeffrey C. Roberts,
• Robert P. Lemieux and
• Frank Giesselmann

Beilstein J. Org. Chem. 2012, 8, 1118–1125, doi:10.3762/bjoc.8.124

• and a narrow higher-ordered smectic phase. Its molecular length was determined by molecular modelling as 50.6 Å. The component with short molecular length is the asymmetric compound 2-(4-butoxyphenyl)-5-octyloxypyrimidine (2PhP) [4]. It exhibits the typical liquid-crystalline phase sequence of nematic

• , smectic A and smectic C phases. Its molecular length is 25.6 Å, according to molecular modelling, which results in a PhP16/2PhP length ratio of almost 2. First, the phase diagram of the system PhP16/2PhP was determined (Figure 3). This phase diagram is very similar to those reported in our earlier studies

• Å obtained by molecular modelling. In conclusion, the material PhP16 shows a first-order phase transition from the tilted SmC phase to the tilted SmF phase at the transition temperature Tc. Conclusion The investigations of the phase diagram of the two phenylpyrimidines PhP16 and 2PhP with a length

Fifty years of oxacalix[3]arenes: A review

• Kevin Cottet,
• Paula M. Marcos and
• Peter J. Cragg

Beilstein J. Org. Chem. 2012, 8, 201–226, doi:10.3762/bjoc.8.22

• to bind to C60 with a Kassoc of 35.5 M−1 in toluene at 25 °C; however, when methylated on the lower rim, no binding was observed. Molecular modelling was employed to illustrate how the shallow cavity of 3a allowed for optimum interactions between the oxacalix[3]arene aromatic rings and C60. While

Laterally substituted symmetric and nonsymmetric salicylideneimine-based bent-core mesogens

• Sonja Findeisen-Tandel,
• Wolfgang Weissflog,
• Ute Baumeister,
• Gerhard Pelzl,
• H. N. Shreenivasa Murthy and
• Channabasaveshwar V. Yelamaggad

Beilstein J. Org. Chem. 2012, 8, 129–154, doi:10.3762/bjoc.8.15

• scattering in the wide-angle region indicating a simple layer structure without in-plane ordering. The layer spacing of 3.8 nm is clearly smaller than the molecular length L = 5.4 nm as estimated by commercial molecular modelling software (Cerius 2) and thus from cosθ = d/L = 3.8 nm/5.4 nm a tilt angle of

Meta-metallation of N,N-dimethylaniline: Contrasting direct sodium-mediated zincation with indirect sodiation-dialkylzinc co-complexation

• David R. Armstrong,
• Liam Balloch,
• Eva Hevia,
• Alan R. Kennedy,
• Robert E. Mulvey,
• Charles T. O'Hara and
• Stuart D. Robertson

Beilstein J. Org. Chem. 2011, 7, 1234–1248, doi:10.3762/bjoc.7.144

• energetically preferred product (relative energy: 0.00 kcal mol−1) with the presence of a Na–N interaction helping its stability. Closely following is the methyl isomer (at 1.61 kcal mol−1) but destabilised are the meta- and para-isomers (by 8.60 and 8.71 kcal mol−1, respectively). On modelling the introduction

• increase in the Na–N(TMEDA) bond lengths from 2.521 and 2.533Å to 2.604 to 2.674 Å. Through these modelling studies, ortho-deprotonation and dimerisation is found to be the energetically preferred metallation pathway by the homometallic reagent, the overall reaction found to be exothermic by −47.55 kcal

• 6A is destabilised further (at 4.32 kcal mol−1); and the least stable of all is metallation at the methyl group (at 9.01 kcal mol−1). Hence in the synergic twofold metal system, the meta- and para-regioisomers are the thermodynamic products. Modelling studies reveal all four deprotonations to be