Studying specificity in protein–glycosaminoglycan recognition with umbrella sampling

• Mateusz Marcisz,
• Sebastian Anila,
• Margrethe Gaardløs,
• Martin Zacharias and
• Sergey A. Samsonov

Beilstein J. Org. Chem. 2023, 19, 1933–1946, doi:10.3762/bjoc.19.144

• regulation of cell growth, proliferation and promotion of cell adhesion, anticoagulation, and wound repair [6][7][8][9]. All these processes are mediated through their direct interactions with diverse protein targets such as collagens, chemokines [10][11], and growth factors [12][13][14], which makes them

Opening up connectivity between documents, structures and bioactivity

• Christopher Southan

Beilstein J. Org. Chem. 2020, 16, 596–606, doi:10.3762/bjoc.16.54

• . However, we will need to await the technical applicability in respect to DARCP capture to see if this opens up connectivity. Keywords: activity data; databases; drug discovery; chemical structures; protein targets; Introduction This article assesses a key aspect of data sharing that has the potential to

A toolbox of molecular photoswitches to modulate the CXCR3 chemokine receptor with light

• Xavier Gómez-Santacana,
• Sabrina M. de Munnik,
• Tamara A. M. Mocking,
• Niels J. Hauwert,
• Shanliang Sun,
• Prashanna Vijayachandran,
• Iwan J. P. de Esch,
• Henry F. Vischer,
• Maikel Wijtmans and
• Rob Leurs

Beilstein J. Org. Chem. 2019, 15, 2509–2523, doi:10.3762/bjoc.15.244

• activity and physiological events with light. A number of protein targets have been explored with photochromic small-molecule ligands, such as ion channels, microtubules, enzymes and GPCRs (G protein-coupled receptors) [1][10]. We focus our photopharmacology research on GPCRs [3][7][11], which constitute a

Carbohydrate inhibitors of cholera toxin

• Vajinder Kumar and
• W. Bruce Turnbull

Beilstein J. Org. Chem. 2018, 14, 484–498, doi:10.3762/bjoc.14.34

• weakly binding) monovalent inhibitors [30][31]. Multivalent ligands have been long applied to a wide range of protein targets [43][44][45]. By having an inhibitor that may bind simultaneously with multiple binding sites, the dissociation rate of the complex is effectively reduced. Even if any individual

Stimuli-responsive oligonucleotides in prodrug-based approaches for gene silencing

• Françoise Debart,
• Christelle Dupouy and
• Jean-Jacques Vasseur

Beilstein J. Org. Chem. 2018, 14, 436–469, doi:10.3762/bjoc.14.32

A speedy route to sterically encumbered, benzene-fused derivatives of privileged, naturally occurring hexahydropyrrolo[1,2-b]isoquinoline

• Olga Bakulina,
• Alexander Ivanov,
• Vitalii Suslonov,
• Dmitry Dar’in and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2017, 13, 1413–1424, doi:10.3762/bjoc.13.138

• small molecules with protein targets and lower off-target effects. The presence of quaternary carbons is characteristic of the natural products domain and is also gaining prominence in medicinal chemistry [30]. Herein, we disclose the results obtained and observations made in the course of our attempt

Biomimetic molecular design tools that learn, evolve, and adapt

• David A Winkler

Beilstein J. Org. Chem. 2017, 13, 1288–1302, doi:10.3762/bjoc.13.125

• targets [25]. Table 1 summarizes the prediction performance of deep neural networks (DNN) and (shallow) Bayesian regularized neural networks (BNN) for very large sets of organic drug-like molecules screened against fifteen protein targets [25]. Good predictions have low RMS errors (RMSE) or standard error

Fluorinated cyclohexanes: Synthesis of amine building blocks of the all-cis 2,3,5,6-tetrafluorocyclohexylamine motif

• Tetiana Bykova,
• Nawaf Al-Maharik,
• Alexandra M. Z. Slawin and
• David O'Hagan

Beilstein J. Org. Chem. 2017, 13, 728–733, doi:10.3762/bjoc.13.72

• the molecular dipole is 5.2 D [2]. The motif has the unique property of inducing facial polarity to the ring system [2][7]. The nature of the interaction of this ring system with protein targets remains to be examined, and its incorporation into organic materials is in its infancy. Access to this

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

• enhancement. For example, the targeting of flexible protein receptors with ligands attached to a rigid DNA-backbone has been reported to be unsuccessful and no preferred ligand distance was found for this “molecular ruler” for flexible divalent protein targets [4]. Recently, we have introduced multivalent

• observed differences on a microscopic level and to derive general principles for the design of optimized multivalent ligands of flexible protein targets. Results and Discussion Selection of a bivalent protein receptor as a target As a representative example for a protein containing a bivalent domain

A small azide-modified thiazole-based reporter molecule for fluorescence and mass spectrometric detection

• Stefanie Wolfram,
• Hendryk Würfel,
• Stefanie H. Habenicht,
• Christine Lembke,
• Phillipp Richter,
• Eckhard Birckner,
• Rainer Beckert and
• Georg Pohnert

Beilstein J. Org. Chem. 2014, 10, 2470–2479, doi:10.3762/bjoc.10.258

• analysis of proteins is the activity-based protein profiling (ABPP) [11][12]. This proteomic strategy uses small probes designed to target active members of enzyme families [13]. These are often based on natural products to investigate their protein targets and eventually their mode of action [14][15

Synthesis and in silico screening of a library of β-carboline-containing compounds

• Kay M. Brummond,
• John R. Goodell,
• Matthew G. LaPorte,
• Lirong Wang and
• Xiang-Qun Xie

Beilstein J. Org. Chem. 2012, 8, 1048–1058, doi:10.3762/bjoc.8.117

• (PDB) and ChEMBL, it is possible to map new compounds into existing chemical space and to predict protein targets for new compounds, for which there are two complementary strategies that can be implemented. One is a structure-based docking strategy, in which a query compound is fit into a series of

• , and allenyl precursors 4, 6{1–16}, 9{1–4} to identify potential protein targets [11]. Protein structures were downloaded from the PDB [12] and the analysis was limited to a selection of the 607 proteins defined as “druggable” targets, in order to reduce computational time [13]. (The complete listing

• site of each protein was defined by the corresponding residues around the cocrystallized ligands. In-house algorithms were used to evaluate ligand-docking efficiency, and docking scores were used to assess and rank the protein targets. A portion of the protein-scoring matrix is illustrated in Figure 3

Synthetic glycopeptides and glycoproteins with applications in biological research

• Ulrika Westerlind

Beilstein J. Org. Chem. 2012, 8, 804–818, doi:10.3762/bjoc.8.90

• synthetic glycoproteins. Since the discovery of native chemical ligation (NCL) by Kent and co-workers, numerous efforts have been made to prepare challenging protein targets [39][40][41][42][43][44]. In the NCL method, a native amide bond is formed by coupling of a C-terminal thioester with the N-terminal

• development of methods in the synthesis of homogenous glycoproteins may result in new therapeutic applications. Better understanding of protein glycosylation will help to identify new protein targets for immunotherapy. The synthesis and application of glycopeptide microarrays is an upcoming topic, which will