Applications of microscopy and small angle scattering techniques for the characterisation of supramolecular gels

• Connor R. M. MacDonald and
• Emily R. Draper

Beilstein J. Org. Chem. 2024, 20, 2608–2634, doi:10.3762/bjoc.20.220

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

• . Several experimental techniques, including NMR, X-ray crystallography and Cryo-EM, can provide critical information for the characterisation of protein structure and conformation. Their widespread and wisely use permitted to experimentally determine the structures of around 200,000 proteins [78], all

• experimental data. Tools for protein structure prediction Due to the vast conformational space and a complex energy function, protein structure prediction (PSP) is a computationally challenging task. Homology modelling is a template-based PSP that may be used to predict the 3D structure of a protein based on

• modelling, and some of the most popular include: 1. AlphaFold2 [88]: It is an open-access protein structure prediction system based on artificial intelligence and machine learning. It is based on a neural network that can predict the 3D protein structure at a high accuracy level. The AlphaFold solution is

Characterization of a new fusicoccane-type diterpene synthase and an associated P450 enzyme

• Jia-Hua Huang,
• Jian-Ming Lv,
• Liang-Yan Xiao,
• Qian Xu,
• Fu-Long Lin,
• Gao-Qian Wang,
• Guo-Dong Chen,
• Sheng-Ying Qin,
• Dan Hu and
• Hao Gao

Beilstein J. Org. Chem. 2022, 18, 1396–1402, doi:10.3762/bjoc.18.144

• might adopt a similar strategy as MgMS to initiate C2,6 cyclization though protonation at C2 by bulky water. To obtain further insights into the C2,6-cyclization process of TadA, its three-dimensional (3D) protein structure was constructed with SWISS-MODEL using PaFS (PDB entry 5er8) as the template

Computational model predicts protein binding sites of a luminescent ligand equipped with guanidiniocarbonyl-pyrrole groups

• Neda Rafieiolhosseini,
• Matthias Killa,
• Thorben Neumann,
• Niklas Tötsch,
• Jean-Noël Grad,
• Alexander Höing,
• Thies Dirksmeyer,
• Jochen Niemeyer,
• Christian Ottmann,
• Shirley K. Knauer,
• Michael Giese,
• Jens Voskuhl and
• Daniel Hoffmann

Beilstein J. Org. Chem. 2022, 18, 1322–1331, doi:10.3762/bjoc.18.137

• two binding grooves for protein ligands, e.g., the C-Raf peptides (yellow). The structure is based on PDB entry 4IHL [20]. Workflow of the computational approach used in this study. The protein structure and the structure of the ligand fragments are the required inputs. Charges and radii are assigned

Cytochrome P450 monooxygenase-mediated tailoring of triterpenoids and steroids in plants

• Karan Malhotra and
• Jakob Franke

Beilstein J. Org. Chem. 2022, 18, 1289–1310, doi:10.3762/bjoc.18.135

• combination with ground-breaking machine learning approaches for protein structure prediction such as AlphaFold2 [108], we anticipate that the catalytic repertoire of CYPs will be exploited much more for the biotechnological production of tailor-made triterpenoids and steroids in the near future. We hope that

Biochemistry of fluoroprolines: the prospect of making fluorine a bioelement

• Vladimir Kubyshkin,
• Rebecca Davis and
• Nediljko Budisa

Beilstein J. Org. Chem. 2021, 17, 439–460, doi:10.3762/bjoc.17.40

• organisms? In protein evolution, mutations obey a simple "similar replaces similar" rule since the disruption of the resulting protein structure is minimized by the modest changes in the amino acid backbone. Hence, when global substitution of proline is aimed at, it should possibly be ascribed to its

• use in protein engineering. The "freezing" of certain proline pucker conformations due to stereospecific fluorination has an effect on the packing within a protein structure as well as the backbone folding parameters (vide infra). 2.5 Thermodynamics of the amide rotation Another special feature of

• fluoroproline-containing sites, which alters the accommodation of the protein in the chaperone pockets. Furthermore, the proline-to-fluoroproline replacement may generate disturbances in the protein structure and stability, as discussed in the next sections. 5 The structural contexts of fluoroprolines in

¹⁹F NMR as a tool in chemical biology

• Diana Gimenez,
• Aoife Phelan,
• Cormac D. Murphy and
• Steven L. Cobb

Beilstein J. Org. Chem. 2021, 17, 293–318, doi:10.3762/bjoc.17.28

• biosynthesis and biodegradation of fluorinated organic compounds is also described. Keywords: biotransformation; chemical biology; fluorine; 19F NMR; probes; protein structure; Introduction Although fluorine is abundant in the environment, it is not a nutrient nor is it a feature of biochemistry for most

• for studying both protein structure and conformational changes within proteins [47]. For additional information on the development of the field of 19F NMR protein studies readers are encouraged to consult the excellent earlier reviews written by Gerig [48] and Danielson and Falke [49]. However, over

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

• microscopy (cryo-EM) [14]. Traditionally, X-ray crystallography was the preferred method to solve the protein structure and determine protein–protein interfaces. However, protein crystallography has the limitation that some protein assemblies have a low diffraction quality and are difficult to crystallise

• variant can have a different cargo while maintaining homogeneity delivered by the protein structure [103]. Conclusion The discovery of PPIs and their mechanisms is an important avenue for understanding how protein–protein complexes function within the cell. In this minireview, we outlined some of the

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

• mucin octapeptide showed that the peptide conformation depended on the extent of glycosylation. Glycosylation induces small changes in protein structure and shifts it from a random to a more turn-like structure [26]. Kirnasky et al. noted that O-glycosylation slightly affected the conformational

Tools for generating and analyzing glycan microarray data

• Akul Y. Mehta,
• Jamie Heimburg-Molinaro and
• Richard D. Cummings

Beilstein J. Org. Chem. 2020, 16, 2260–2271, doi:10.3762/bjoc.16.187

• thus provides a unique one-stop solution to cross referencing glycan microarray data alongside protein structure. 2. Gly-Spec (Grafting): Status: Available. Address: http://glycam.org/djdev/grafting/. Description: Gly-Spec (Grafting) uses structural data to predict glycan microarray binding [52]. In

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

• 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

Synthesis and biological evaluation of truncated derivatives of abyssomicin C as antibacterial agents

• Leticia Monjas,
• Peter Fodran,
• Johanna Kollback,
• Carlo Cassani,
• Thomas Olsson,
• Maja Genheden,
• D. G. Joakim Larsson and
• Carl-Johan Wallentin

Beilstein J. Org. Chem. 2019, 15, 1468–1474, doi:10.3762/bjoc.15.147

• resulting protein conformation was allowed to relax to ensure that the found conformation was an energy minimum. This protein structure was then used for docking of ligands using Glide [22][23][24]. Glide XP docking positioned both AbC and the analog atrop-O-benzyl-desmethyl-abyssomicin C with low energy

Aqueous olefin metathesis: recent developments and applications

• Valerio Sabatino and
• Thomas R. Ward

Beilstein J. Org. Chem. 2019, 15, 445–468, doi:10.3762/bjoc.15.39

• -Chymotrypsin interacts with catalyst 66 through supramolecular interactions followed by covalent nucleophilic attack to afford ArM 3. Assembling an artificial metathase (ArM 4) based on the small heat shock protein from M. Jannaschii (MjHSP). The protein structure is based on the atomic coordinates in PDB

• modification of proteins via aqueous cross-metathesis. The protein structure is based on the atomic coordinates in PDB entry 1NDQ. a) Allyl homocysteine (Ahc)-modified proteins as CM substrates. b) Incorporation of Ahc in the Fc portion of IgG in human cells (HEK 293T) and CM reaction with 84. On-DNA cross

Olefin metathesis catalysts embedded in β-barrel proteins: creating artificial metalloproteins for olefin metathesis

• Daniel F. Sauer,
• Johannes Schiffels,
• Takashi Hayashi,
• Ulrich Schwaneberg and
• Jun Okuda

Beilstein J. Org. Chem. 2018, 14, 2861–2871, doi:10.3762/bjoc.14.265

• present as minor motifs or even dominate the overall protein structure [33][34]. Small β-barrels such as lipocalins (i.e., transporters of small hydrophobic molecules that play vital roles in many biological processes [35]) or heme-containing nitrophorins/nitrobindins of the all-β-barrel type (involved in

• membrane. TIM-barrels (named after triosephosphate isomerase, TIM), in turn, contain both α- and β-structures, i.e., a β-barrel structure (eight strands) enclosed by a series of eight α- helices. The TIM-barrel represents a very common – yet evolutionarily diverse – protein structure [40]. While following

• – called unfolded FhuA – and facilitates the access of the GH-type catalysts to the cysteine C545 [59]. The resulting biohybrid catalysts Ru-4/5/6@FhuA* were washed repeatedly to remove unbound catalyst. The protein structure was restored (“renaturation”) leading to the refolded biohybrid catalysts Ru-4/5

Preparation of trinucleotide phosphoramidites as synthons for the synthesis of gene libraries

• Ruth Suchsland,
• Bettina Appel and
• Sabine Müller

Beilstein J. Org. Chem. 2018, 14, 397–406, doi:10.3762/bjoc.14.28

• protein structure and the mechanism of action. On the opposite, directed evolution relies on the selection of a mutant with predefined properties from a random protein library. This strategy is advantageous over the rational design; whenever molecular properties of proteins are investigated that are not

2-Methyl-2,4-pentanediol (MPD) boosts as detergent-substitute the performance of ß-barrel hybrid catalyst for phenylacetylene polymerization

• Julia Kinzel,
• Daniel F. Sauer,
• Marco Bocola,
• Marcus Arlt,
• Tayebeh Mirzaei Garakani,
• Andreas Thiel,
• Klaus Beckerle,
• Tino Polen,
• Jun Okuda and
• Ulrich Schwaneberg

Beilstein J. Org. Chem. 2017, 13, 1498–1506, doi:10.3762/bjoc.13.148

• molecules as stabilizing cosolvent to investigate the molecular dynamics of protein structure stabilization, how a small amphiphilic molecule could stabilize a transmembrane protein such as FhuA ΔCVFtev. All simulations started with a random distribution of MPD, but after a few nanoseconds, the MPD

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

• , besides being suitable for the study of heterogenous systems that are unlikely to crystallise. Furthermore, the experiments in solution allow the effect of other factors, such as pH, ion concentration, or temperature, on the overall protein structure to be studied. Samples for structure analysis should be

From chemical metabolism to life: the origin of the genetic coding process

• Antoine Danchin

Beilstein J. Org. Chem. 2017, 13, 1119–1135, doi:10.3762/bjoc.13.111

• centrioles, which undergo exact duplication in each generation. The process that drives this duplication of a protein structure is still a matter of speculation [43]. Centrioles are cylindrical protein complexes with a nine-fold symmetry that is broken with a very precise timing when cells prepare to produce

O-Alkylated heavy atom carbohydrate probes for protein X-ray crystallography: Studies towards the synthesis of methyl 2-O-methyl-L-selenofucopyranoside

• Roman Sommer,
• Dirk Hauck,
• Annabelle Varrot,
• Anne Imberty,
• Markus Künzler and
• Alexander Titz

Beilstein J. Org. Chem. 2016, 12, 2828–2833, doi:10.3762/bjoc.12.282

• -glucosamine, have been described in rats as metabolites for detoxifying inorganic selenite intake [12][13]. Selenium-containing compounds are also widely used as tools for protein X-ray crystallography in structural biology. The determination of a protein structure depends on the correct phase recovering

Synthesis of spiro[isoindole-1,5’-isoxazolidin]-3(2H)-ones as potential inhibitors of the MDM2-p53 interaction

• Salvatore V. Giofrè,
• Santa Cirmi,
• Raffaella Mancuso,
• Francesco Nicolò,
• Giuseppe Lanza,
• Laura Legnani,
• Agata Campisi,
• Maria A. Chiacchio,
• Michele Navarra,
• Bartolo Gabriele and
• Roberto Romeo

Beilstein J. Org. Chem. 2016, 12, 2793–2807, doi:10.3762/bjoc.12.278

• coordinates of the complex of the MI63-analogue with MDM2 [53][54]. The protein structure PDB ID 3LBL was chosen as the reference receptor because its ligand had high binding affinity and high resolution (1.6 Å). Docking studies were performed using AutoDock4.2 and both enantiomers of compounds 6a–f were

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

• methods are discussed. Advances in virtual high-throughput screening, protein structure prediction methods, protein–ligand docking, pharmacophore modeling and QSAR techniques are reviewed. Keywords: ADME; computer-aided drug design; docking; free energy; high-throughput screening; LBDD; lead optimization

• of glaucoma and was developed using structure-based tools (Figure 3) [7][8]. Protein structure determination All structure-based methods rely on the three-dimensional target structure. The most common way to determine a protein structure is by X-ray crystallography and NMR spectroscopy. Recently

• in determining their structures [20]. One of the disadvantages of NMR is that it generally is limitated to smaller proteins. Attempts are continuously being made to overcome these challenges and limitations of experimental methods [21]. SBDD methods rely on the protein structure and in the cases

Artificial Diels–Alderase based on the transmembrane protein FhuA

• Hassan Osseili,
• Daniel F. Sauer,
• Klaus Beckerle,
• Marcus Arlt,
• Tomoki Himiyama,
• Tino Polen,
• Akira Onoda,
• Ulrich Schwaneberg,
• Takashi Hayashi and
• Jun Okuda

Beilstein J. Org. Chem. 2016, 12, 1314–1321, doi:10.3762/bjoc.12.124

• dialysis against SDS-solution, excess catalyst 10–12 was removed. Additional 3 days of dialysis against PE-PEG solution renatured the protein structure to give the expected β-barrel structure, as indicated by CD spectra (Figure 1). The CD spectra show a minimum at around 215 nm and a maximum at 195 nm, as

Recent highlights in biosynthesis research using stable isotopes

• Jan Rinkel and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2015, 11, 2493–2508, doi:10.3762/bjoc.11.271

• black dots. KS: keto-synthase; B: branching domain; ACP: acyl carrier protein. Structure of coelimycin P1 (8) and proposed biosynthetic formation from the putative PKS produced aldehyde 5 via cyclized bisepoxide 7. Structure of trioxacarcin A (9) with highlighted carbon origins of the polyketide core

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

• ). The PA-IL protein structure has been inferred from the Protein Data Bank (PDB code 4ljh). List of photoswitchable precision glycooligomers obtained via solid phase polymer synthesis. IC50 values obtained by SPR inhibition/competition assays of the photoswitchable glycooligomers and control structures

A bisazobenzene crosslinker that isomerizes with visible light

• Subhas Samanta,
• Harris I. Qureshi and
• G. Andrew Woolley

Beilstein J. Org. Chem. 2012, 8, 2184–2190, doi:10.3762/bjoc.8.246

• been used for reversible manipulation of biological targets, including peptide and protein structure and function [1][2][3][4][5][6][7][8][9][10][11][12], enzyme activities [13][14][15][16][17], oligonucleotide functions [18][19][20], and ion-channel activities [21][22][23]. A quantitative analysis of