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

• efficient modulators of 14-3-3 protein–protein interactions (PPIs) [3][4]. 14-3-3 PPIs, which refer to the binding interactions of 14-3-3 proteins with hundreds of “client” proteins, are associated with many diseases, such as cancer and neurodegenerative diseases [3][4]. As a result, lots of attempts

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

• option to modulate, inhibit, or stabilize protein–protein interactions (PPI) is the use of specific supramolecular ligands [7][8]. One well-known example of efficient protein binders is the so-called guanidiniocarbonyl-pyrrole (GCP) developed 20 years ago by Schmuck et al. [9]. These compounds are known

Facile and diastereoselective arylation of the privileged 1,4-dihydroisoquinolin-3(2H)-one scaffold

• Dmitry Dar’in,
• Grigory Kantin,
• Alexander Bunev and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2022, 18, 1070–1078, doi:10.3762/bjoc.18.109

• probe for protein–protein interactions, including oncogenic ones [26]. As the first step towards biological characterization of compounds 9, they were screened for cytotoxicity against the NCI-H460 lung carcinoma cell line. The most potent cytotoxic agent (9j) reduced the number of viable cells by >95

Unusual highly diastereoselective Rh(II)-catalyzed dimerization of 3-diazo-2-arylidenesuccinimides provides access to a new dibenzazulene scaffold

• Anastasia Vepreva,
• Alexander S. Bunev,
• Andrey Yu. Kudinov,
• Grigory Kantin,
• Mikhail Krasavin and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2022, 18, 533–538, doi:10.3762/bjoc.18.55

• diastereomer 2a is indicative of a sequence of concerted processes with an unambiguous stereochemistry control at each step where stereogenic centers are formed. Dibenzoazulenodipyrroles 2 have a pronounced three-dimensional character which make this chemotype promising as probe for protein–protein

• interactions, including oncogenic ones [18]. As the first step towards biological characterization of compounds 2, they were screened for cytotoxicity against the A549 human lung adenocarcinoma cell line. Among the eleven compounds, N-aryl analogs 2a–e, 2h, and 2j had no effect on the cancer cell viability

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

• stapling techniques to stabilise α-helical secondary structure motifs of peptides led to the design of modulators of protein–protein interactions, which had been considered undruggable for a long time. We disclose a novel approach towards peptide stapling utilising macrocyclisation by late-stage Suzuki

• + 7 for two helix turns, respectively, followed by Ru-catalysed cross-linking [7]. By this robust and reliable approach, a library of stapled peptides was generated influencing diverse α-helical dominated protein–protein interactions (PPI) spanning pathways involved in cancer, infectious diseases

A systems-based framework to computationally describe putative transcription factors and signaling pathways regulating glycan biosynthesis

• Theodore Groth,
• Rudiyanto Gunawan and
• Sriram Neelamegham

Beilstein J. Org. Chem. 2021, 17, 1712–1724, doi:10.3762/bjoc.17.119

• the activity of promoter and enhancer regions through cap analysis of gene expression (CAGE), TF motif instances, and expression quantitative trait loci (eQTL) to evaluate weights (evidence scores) for TF–gene isoform relationships; and iii) integration of TF-binding motifs, protein–protein

• interactions, and coexpression networks using data from GTEx and a method called PANDAS [42]. Such analyses represent next steps in this project, as extensive data harmonization is required for cross-platform validation. Care should be taken when integrating these data, however, as the kind of omics data

Antiviral therapy in shrimp through plant virus VLP containing VP28 dsRNA against WSSV

• Santiago Ramos-Carreño,
• Ivone Giffard-Mena,
• Jose N. Zamudio-Ocadiz,
• Alfredo Nuñez-Rivera,
• Ricardo Valencia-Yañez,
• Jaime Ruiz-Garcia,
• Maria Teresa Viana and
• Ruben D. Cadena-Nava

Beilstein J. Org. Chem. 2021, 17, 1360–1373, doi:10.3762/bjoc.17.95

• degraded by nucleases [42][53]. The appropriate synthesis of VLP-dsRNAvp28 was only obtained after the sample was acidified by dialysis in virus buffer (pH 4.5). After acidification no more aberrant and complex capsids were observed (Figure 2A, images c and d). The low pH promotes protein–protein

• interactions and allows the stable forms of VLPs [54]. The TEM micrographs revealed two types of VLPs shapes: the icosahedral and the long tubular structures. The individual VLPs with a spherical (icosahedral) shape are likely to have few ssRNA molecules, due to the low contamination of the RNAi stock with

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

• fluorinated probes and their incorporation into macromolecules, the application of 19F NMR to monitor protein–protein interactions, protein–ligand interactions, physiologically relevant ions and in the structural analysis of proteins and nucleic acids. The continued relevance of the technique to investigate

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

• knowledge of protein–protein interactions, common characterisation methods to characterise them, and their role in protein complex formation with some examples. A deep understanding of protein–protein interactions and their molecular interactions is important for a number of applications, including drug

• design. Protein–protein interactions and their discovery are thus an interesting avenue for understanding how protein complexes, which make up the majority of proteins, work. Keywords: characterisation methods; heterooligomeric complex; homooligomeric complex; molecular interactions; protein–protein

• protein–protein interactions (PPIs). Hedin characterised the first PPI with trypsin and antitrypsin in 1906 [1], which provided a landmark for the awareness of what role PPIs have in cellular physiology. In fact, even though individual proteins perform essential functions, their effectiveness in the cell

Selected peptide-based fluorescent probes for biological applications

• Debabrata Maity

Beilstein J. Org. Chem. 2020, 16, 2971–2982, doi:10.3762/bjoc.16.247

• reliable design strategies which are useful in number of applications including analyte detection, understanding molecular details of protein–peptide and protein–protein interactions. Recent developments of novel fluorophores and tailor-made receptors have opened the possibility of designing peptide-based

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

• [2][3]; the level of N-glycan expression regulates the adhesiveness of a cell [4]; glycosylation also plays a role in immune function [5] and cellular signalling [5][6]. At the forefront, glycosylation plays a significant role in influencing protein–protein interactions. For example, the influenza

NMR Spectroscopy of supramolecular chemistry on protein surfaces

• Peter Bayer,
• Anja Matena and
• Christine Beuck

Beilstein J. Org. Chem. 2020, 16, 2505–2522, doi:10.3762/bjoc.16.203

• modulate protein–protein interactions. Here we present NMR methods that have been applied to characterize these molecular interactions and discuss the challenges of this endeavor. Keywords: molecular recognition; NMR; protein ligand interaction; protein surfaces; supramolecular chemistry; Introduction In

• recent years, the focus of biochemical research and drug development has shifted from the inhibition of single enzymes to targeting protein-protein interactions [1][2], which play key roles in cellular function and dysfunction [3][4]. Enzymes usually bind their substrates in deep pockets with specific

• formed between the charged head group of the encapsulated amino acid and one of the phosphate moieties attached to the tweezer’s central benzene ring [5]. Supramolecular tweezers have not only proven to be interesting tools to modulate protein–protein interactions [6][7], reverse amyloid fibril formation

Muyocopronones A and B: azaphilones from the endophytic fungus Muyocopron laterale

• Ken-ichi Nakashima,
• Junko Tomida,
• Tomoe Tsuboi,
• Yoshiaki Kawamura and
• Makoto Inoue

Beilstein J. Org. Chem. 2020, 16, 2100–2107, doi:10.3762/bjoc.16.177

• fungus; modified Mosher’s method; Muyocopron laterale; polyketides; Introduction Azaphilones, which are a class of fungal polyketides with diverse structures, have received growing attention due to their various biological activities, such as the inhibition of some protein–protein interactions [1][2

Fluorinated phenylalanines: synthesis and pharmaceutical applications

• Laila F. Awad and
• Mohammed Salah Ayoup

Beilstein J. Org. Chem. 2020, 16, 1022–1050, doi:10.3762/bjoc.16.91

• the properties of peptides and proteins [5][6][7], influencing aspects such as protein folding, protein–protein interactions, ribosomal translation, lipophilicity, acidity/basicity, optimal pH, stability, thermal stability, and therapeutic properties [8][9][10]. This extends to metabolic properties of

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

• molecular scaffolds to develop chemical libraries can increase the chance of finding compounds able to address the so-called “undruggable” targets, such as protein–protein interactions [1]. In this context, molecules containing one or more rings are of primary interest, as they will suffer a reduced

• generation of high-quality small molecule collections, taking advantage of the stereochemical diversity, and of their three-dimensional shape and structural bias to develop lead compounds, specifically in the field of protein–protein interactions [3][4][5][6]. Spiranic rings such as spiroketals are present

Synthesis and characterization of bis(4-amino-2-bromo-6-methoxy)azobenzene derivatives

• David Martínez-López,
• Amirhossein Babalhavaeji,
• Diego Sampedro and
• G. Andrew Woolley

Beilstein J. Org. Chem. 2019, 15, 3000–3008, doi:10.3762/bjoc.15.296

• isomerization cycles [10]. Efforts to apply 1 to photocontrol protein–protein interactions have recently been reported [13]. Despite the usefulness of 1 as a photoswitch, compounds undergoing photoisomerization at longer wavelengths (>700 nm) would be valuable since the penetration of light through tissue is

Solid-phase synthesis of biaryl bicyclic peptides containing a 3-aryltyrosine or a 4-arylphenylalanine moiety

• Iteng Ng-Choi,
• Àngel Oliveras,
• Lidia Feliu and
• Marta Planas

Beilstein J. Org. Chem. 2019, 15, 761–768, doi:10.3762/bjoc.15.72

• protein–protein interactions [1][2][3][4][5][6][7][8][9]. These advantageous attributes rise from the rigidity of their conformational structure and from the low susceptibility to protease degradation of the cyclic backbone. There is a wide range of methods for the macrocyclization of linear peptides [1

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

• the solid phase), this technology has been exploited to disrupt protein–protein interactions (PPIs) in cancer cells [94][95][96]. Aileron Therapeutics recently launched a stapled peptide platform aiming at developing molecules like ALRN-6924, a stapled peptide that interacts with p53 inhibitors MDMX

Synthesis of C₃-symmetric star-shaped molecules containing α-amino acids and dipeptides via Negishi coupling as a key step

• Sambasivarao Kotha and
• Saidulu Todeti

Beilstein J. Org. Chem. 2019, 15, 371–377, doi:10.3762/bjoc.15.33

• the structural and chemical nature of protein–protein interactions, synthetic peptides and unnatural AAAs [8][9][10][11][12][13][14][15] can be useful as molecular tools. Moreover, C3-symmetric peptides are valuable in studying the molecular interactions involving proteins that are derived from

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

• reducing the burden of multidrug-resistant microorganisms. Protein–protein interactions (PPIs) are involved in a myriad of vital cellular processes and have become an attractive target to treat diseases. Therefore, targeting PPI networks in bacteria may offer a new and unconventional point of intervention

• represent an alternative lead discovery strategy to obtain new anti-infective molecules. Keywords: new antibiotics; protein–protein interactions; resistance; Introduction Bacterial infections are not only one of the most frequent diseases in humans and livestock, but also one of the top ten causes of

• therapies with novel unconventional targets [9], such as protein–protein interactions [10][11]. This review covers the recent medicinal chemistry efforts towards the discovery of antibacterial molecules that disrupt protein–protein interactions (PPIs) by interacting directly to the protein–protein binding

One-pot sequential synthesis of tetrasubstituted thiophenes via sulfur ylide-like intermediates

• Jun Ki Kim,
• Hwan Jung Lim,
• Kyung Chae Jeong and
• Seong Jun Park

Beilstein J. Org. Chem. 2018, 14, 243–252, doi:10.3762/bjoc.14.16

• reported an effective ylide transfer reagent, which led to sulfonium ylide 6 [35][36][37][38]. As part of our ongoing efforts to discover small molecule modulators of protein–protein interactions (PPIs), we are particularly interested in coplanar compounds that mimic β-strand side-chain distributions [39

The use of 4,4,4-trifluorothreonine to stabilize extended peptide structures and mimic β-strands

• Yaochun Xu,
• Isabelle Correia,
• Tap Ha-Duong,
• Nadjib Kihal,
• Jean-Louis Soulier,
• Julia Kaffy,
• Benoît Crousse,
• Olivier Lequin and
• Sandrine Ongeri

Beilstein J. Org. Chem. 2017, 13, 2842–2853, doi:10.3762/bjoc.13.276

• dynamics simulations. CF3-threonine containing pentapeptides are more prone to mimic β-strands than their natural Ser and Thr pentapeptide analogues. The proof of concept that these fluorinated β-strand mimics are able to disrupt protein–protein interactions involving β-sheet structures is provided. The

• CF3-threonine containing pentapeptides interact with the amyloid peptide Aβ1-42 in order to reduce the protein–protein interactions mediating its aggregation process. Keywords: aggregation; beta-sheet; fluorine; peptide; unnatural amino acid; Introduction It is estimated that 20% of administered

• stabilizer of β-strand mimics. Indeed, β-strand mimics have a particular interest as ligand of β-sheet structures and as potential inhibitors of protein–protein interactions involving β-sheet structures [11][12][13]. For example, β-strand mimics have been successfully introduced in inhibitors of amyloid

Hydrolysis, polarity, and conformational impact of C-terminal partially fluorinated ethyl esters in peptide models

• Vladimir Kubyshkin and
• Nediljko Budisa

Beilstein J. Org. Chem. 2017, 13, 2442–2457, doi:10.3762/bjoc.13.241

• measurements can be used to study ligand–protein [12] and protein–protein interactions [13]; membrane proteins [14][15][16] and membrane-associated peptides [17][18]; equilibria among conformations of RNA [19], DNA [20], and peptide nucleic acids (PNA) [21]; and many others. Particularly recent is the

Investigation of the action of poly(ADP-ribose)-synthesising enzymes on NAD⁺ analogues

• Sarah Wallrodt,
• Edward L. Simpson and
• Andreas Marx

Beilstein J. Org. Chem. 2017, 13, 495–501, doi:10.3762/bjoc.13.49

• tankyrases ARTD5 and ARTD6 also exhibit a unique domain structure consisting of multiple ankyrin repeats mediating protein–protein interactions [13]. Tankyrases are involved in telomere homeostasis, Wnt/β-catenin signalling, glucose metabolism, and cell cycle progression [14]. Remarkable efforts have been

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