Activity assays of NnlA homologs suggest the natural product N-nitroglycine is degraded by diverse bacteria

• Kara A. Strickland,
• Brenda Martinez Rodriguez,
• Ashley A. Holland,
• Shelby Wagner,
• Michelle Luna-Alva,
• David E. Graham and
• Jonathan D. Caranto

Beilstein J. Org. Chem. 2024, 20, 830–840, doi:10.3762/bjoc.20.75

• [32]. We sought to identify the heme binding site, but AlphaFold does not model this. However, this AlphaFold model was predicted to bind a heme cofactor by the consensus modeling tool COACH [33]. This protein–ligand model exhibited steric clashes with the heme and protein side chains (data not shown

• NnlA model in Figure 5A. Several of these residues are nearby the predicted heme binding site, which may suggest their importance in NNG binding near the heme. However, many of these residues are either far from the heme or would not orient NNG towards the distal pocket of the heme. Future mutagenesis

Recent developments in the engineered biosynthesis of fungal meroterpenoids

• Zhiyang Quan and
• Takayoshi Awakawa

Beilstein J. Org. Chem. 2024, 20, 578–588, doi:10.3762/bjoc.20.50

• compounds (40, 43, 44, 47, 48, 50, 51, and 53–55) (Figure 7A). In addition, a structure-based mutagenesis study of SptF was performed to further amplify its catalytic potential. Firstly, the hydrophobic residues Ile63, Phe133, and Ile231, which compose the substrate binding site of SptF, were mutated. As a

• change their reaction products depending on the conformation of the terpenoid skeleton, the regiospecificity of the oxidation reaction can be modified by introducing random mutations in the substrate-binding site of αKG-dependent dioxygenase. The αKG-dependent dioxygenase AndA withdraws H-12 of

Switchable molecular tweezers: design and applications

• Pablo Msellem,
• Maksym Dekthiarenko,
• Nihal Hadj Seyd and
• Guillaume Vives

Beilstein J. Org. Chem. 2024, 20, 504–539, doi:10.3762/bjoc.20.45

• tweezers by the first equivalent generating an allosteric binding site specific to a second Hg2+ ion. While the addition of one equivalent of Hg2+ decreased the quantum yield to 0.09, the formation of a bis-coordinated [tweezers-Hg2]4+ complex resulted in a total luminescence quenching (quantum yield <10−3

• using metal complexes as switching units (Figure 20). This concept named “weak link approach” (WLA) [78] uses square planar d8-transition metal complexes with two hemilabile bidentate ligands composed of a strong binding site (phosphorus) and a weaker one (generally sulfur, oxygen, selenium, or nitrogen

• ) that is labile. By default, the complex is in a closed form with the functional units on each ligand facing each other due to the square planar geometry of the complex. By adding a first ancillary ligand (carbon monoxide, chloride,…) that strongly binds to the metal center, one weak binding site is

Green and sustainable approaches for the Friedel–Crafts reaction between aldehydes and indoles

• Periklis X. Kolagkis,
• Eirini M. Galathri and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2024, 20, 379–426, doi:10.3762/bjoc.20.36

• the GPR receptor can aggravate the symptoms of myeloid leukemia. In contrast to most GPR84 agonists which contain long alkyl chains, BIMs are not lipophilic molecules, which allow them to bind to the GPR receptor via an allosteric binding site and modulate GPR84’s rate of expression [2]. One

Elucidating the glycan-binding specificity and structure of Cucumis melo agglutinin, a new R-type lectin

• Jon Lundstrøm,
• Emilie Gillon,
• Valérie Chazalet,
• Nicole Kerekes,
• Antonio Di Maio,
• Ten Feizi,
• Yan Liu,
• Annabelle Varrot and
• Daniel Bojar

Beilstein J. Org. Chem. 2024, 20, 306–320, doi:10.3762/bjoc.20.31

• aligned the individual units of the tandem repeat CBM13 domains, indicated by the N-terminal (34-158) and C-terminal units (162-286) and compared those to the domains of ricin (Figure 1b). R-type lectins have a characteristic Q-x-W structural motif close to their binding site, which is highly conserved

• to elucidate the molecular mechanism that would enable the specific binding of C2-substituted galactose. The natural hypothesis here would be the creation of an additional pocket in the 3D structure of the binding site, accommodating the additional substituent at C2. However, as we observed little to

• (Val6 to Asp132) could be modelled, and unambiguous electron density permitted us to locate and model four cation binding sites (three in each structure) and one sugar binding site (Figure 4a,b and Figure S4, Supporting Information File 2). The complexed structures allowed us to shed light on the

Photoinduced in situ generation of DNA-targeting ligands: DNA-binding and DNA-photodamaging properties of benzo[c]quinolizinium ions

• Julika Schlosser,
• Olga Fedorova,
• Yuri Fedorov and
• Heiko Ihmels

Beilstein J. Org. Chem. 2024, 20, 101–117, doi:10.3762/bjoc.20.11

• delivered without effect to the binding site, where the DNA-binding benzoquinolizinium ligand can then be generated as needed upon irradiation. Notably, the use of light for the activation of photo-controllable DNA ligands offers several advantages because it is easy to apply, traceless, and non-invasive

• within the binding site. The binding mode of the benzo[c]quinolizinium derivatives 3c,e–g with DNA was further examined with circular dichroism (CD) and linear dichroism (LD) spectroscopy (Figure 6 and Supporting Information File 1, Figures S12–S14). Hence, with increasing ligand-DNA ratio (LDR) weak

• binding angle α = 59° between the ligand 3f and the DNA helix, thus indicating a tilted orientation of the ligand relative to the DNA base pairs within the binding site. The DNA-binding ligands were also generated in situ in the presence of DNA. For that purpose, solutions of the styrylpyridines 2d–g and

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

• essential to explain their biological functions. In this study, the umbrella sampling (US) approach is used to pull away a GAG ligand from the binding site and then pull it back in. We analyze the binding interactions between GAGs of three types (heparin, desulfated heparan sulfate, and chondroitin sulfate

• /pdb, [37]). The third complex is known to exist in two different binding poses which are experimentally well established. In this study, the umbrella sampling (US) approach is used to pull away a GAG ligand from the binding site and then pull it back in. The main focus of our study is to evaluate

• RS-REMD (replica exchange with repulsive scaling), an MD-based docking method [41], to assure proper binding poses of the whole ligand and ring puckering and to be consistent with further simulations. The docked ligands cover the binding site the same way as ligands in the experimental structures

Tying a knot between crown ethers and porphyrins

• Maksym Matviyishyn and
• Bartosz Szyszko

Beilstein J. Org. Chem. 2023, 19, 1630–1650, doi:10.3762/bjoc.19.120

• -capped calix[4]pyrrole cavitand 4. The heteroditopic receptor had multiple binding sites, proving efficient in encapsulating a CsF ion pair. The calix[4]arene-crown-6-capped pocket was exploited as an excellent binding site for the Cs+ cation, whereas the calix[4]pyrrole was aligned to trap the fluoride

Synthesis of ether lipids: natural compounds and analogues

• Marco Antônio G. B. Gomes,
• Alicia Bauduin,
• Chloé Le Roux,
• Romain Fouinneteau,
• Wilfried Berthe,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2023, 19, 1299–1369, doi:10.3762/bjoc.19.96

• ). The review of Lemaire et al., dedicated to the synthesis of glycerol ether, is complemental to this review article [57]. Of note, the review of Godfroid and Braquet attempted to decipher the binding site of PAF via a QSAR study [58]. 1.1 Synthesis of PAF and some building blocks The platelet

CO₂ complexation with cyclodextrins

• Cecilie Høgfeldt Jessen,
• Jesper Bendix,
• Theis Brock Nannestad,
• Heloisa Bordallo,
• Martin Jæger Pedersen,
• Christian Marcus Pedersen and
• Mikael Bols

Beilstein J. Org. Chem. 2023, 19, 1021–1027, doi:10.3762/bjoc.19.78

• change in spectrum of 7 provided 7 and CO2 compete for the binding site. To avoid problems with formation of hydrogencarbonate the experiments were conducted in a buffer at pH 3 where only a minor fraction of the carbonic acid (pKa1 = 3.6) is dissociated and since the hydration constant of CO2 is small

Dipeptide analogues of fluorinated aminophosphonic acid sodium salts as moderate competitive inhibitors of cathepsin C

• Karolina Wątroba,
• Małgorzata Pawełczak and
• Marcin Kaźmierczak

Beilstein J. Org. Chem. 2023, 19, 434–439, doi:10.3762/bjoc.19.33

• pocket of the enzyme. In contrast, the S2 pocket preferably accommodates amino acids having short aliphatic side-chains, but also recognizes aromatic amino acids, preferably phenylalanine. To study the structural requirements of the S1 binding site of the enzyme, we synthesized a series of ten dipeptide

Preparation of β-cyclodextrin-based dimers with selectively methylated rims and their use for solubilization of tetracene

• Konstantin Lebedinskiy,
• Volodymyr Lobaz and
• Jindřich Jindřich

Beilstein J. Org. Chem. 2022, 18, 1596–1606, doi:10.3762/bjoc.18.170

• , USA), to the two independent binding sites model. From the fit, the stoichiometry (n), binding enthalpy change (ΔH, kJ·mol−1), affinity constant (Ka, M−1), binding free energy change (ΔG, kJ·mol−1), and binding entropy change (ΔS, J·mol–1·K−1) for the first binding site were calculated. The

• thermodynamic parameters for the second binding site were not discussed but used to subtract the nonlinear residual heat at high molar ratios. Separate titration experiments of pure DMSO to the solution of tetracene in DMSO and DMSO to the solution of water in DMSO were carried out to account for potential

Microelectrode arrays, electrosynthesis, and the optimization of signaling on an inert, stable surface

• Kendra Drayton-White,
• Siyue Liu,
• Yu-Chia Chang,
• Sakashi Uppal and
• Kevin D. Moeller

Beilstein J. Org. Chem. 2022, 18, 1488–1498, doi:10.3762/bjoc.18.156

•  5) [21]. Gαi1 was selected as a positive control for subsequent studies because it can be expressed easily, has roughly 55% homology with the much more difficult to express Gαq [15], and chimeric proteins are available that have Gαi1 modified with a Gαq binding site for YM and FR [22]. R6A was

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

• area above and below the central pore of the dimeric 14-3-3ζ protein is the most probable binding site for the ligand. Moreover, we predict that the position of the ligand is sensitive to the presence of phosphorylated C-Raf peptides. With a series of experiments, we confirmed the computational

• pairs of proteins (Figure 2b). Knowledge of the binding site is of critical importance for a potential bioanalytics application: if 1 would block one or both wells of the ω, it could prevent binding of ligand proteins, whereas a 1 binding site in the outer parts of the ω would not interfere with

• 1.5.2 [41]. To validate our method, we applied it to the QQJ-096/14-3-3/c-Raf complex for which the potential binding site was available from all-atom molecular dynamics simulations in a previous study [26]. Our results for this system are reported in the first part of the Supporting Information File 1

Post-synthesis from Lewis acid–base interaction: an alternative way to generate light and harvest triplet excitons

• Hengjia Liu and
• Guohua Xie

Beilstein J. Org. Chem. 2022, 18, 825–836, doi:10.3762/bjoc.18.83

• determined from the optimized structures of compounds 21 and 22 (Figure 13a) by DFT suggest that pyridine is a better binding site than thiophene [43]. The effect of steric hindrance on the Lewis acid–base binding should not be ignored. If there is large steric hindrance of the Lewis basic molecules, it will

Structural basis for endoperoxide-forming oxygenases

• Takahiro Mori and
• Ikuro Abe

Beilstein J. Org. Chem. 2022, 18, 707–721, doi:10.3762/bjoc.18.71

• observed in typical Fe/2OG-dependent oxygenases (Figure 3A). The Fe(II) is coordinated by His129, Asp131, His205, and 2OG in the binary complex structure of FtmOx1 with 2OG. In this structure, Tyr224 is close to the putative oxygen binding site (Figure 3B). Furthermore, the variants in which Tyr224 is

Heteroleptic metallosupramolecular aggregates/complexation for supramolecular catalysis

• Prodip Howlader and
• Michael Schmittel

Beilstein J. Org. Chem. 2022, 18, 597–630, doi:10.3762/bjoc.18.62

• procedure developed by Sauvage on the basis of topological control [33] has found ample use in the preparation of rotaxane-based machines and devices [34]. A key element is a macrocyclic phenanthroline with an endotopic binding site as it precludes homoleptic complex formation. A further principle

(Phenylamino)pyrimidine-1,2,3-triazole derivatives as analogs of imatinib: searching for novel compounds against chronic myeloid leukemia

• Luiz Claudio Ferreira Pimentel,
• Lucas Villas Boas Hoelz,
• Henayle Fernandes Canzian,
• Frederico Silva Castelo Branco,
• Andressa Paula de Oliveira,
• Vinicius Rangel Campos,
• Floriano Paes Silva Júnior,
• Rafael Ferreira Dantas,
• Jackson Antônio Lamounier Camargos Resende,
• Anna Claudia Cunha,
• Nubia Boechat and
• Mônica Macedo Bastos

Beilstein J. Org. Chem. 2021, 17, 2260–2269, doi:10.3762/bjoc.17.144

• , with IC50 values between 1.0 and 7.3 μM, and were subjected to molecular docking studies. The results suggest that such compounds can interact at the same binding site as imatinib, probably sharing a competitive inhibition mechanism. One compound showed the greatest interaction affinity for BCR-Abl-1

• TKIs that are even more potent than IMT, such as nilotinib [6][7]. These drugs act as inhibitors at the ATP binding site in the inactive form of BCR-Abl-1, preventing the binding of the protein to ATP in a competitive manner and resulting in the interruption of the substrate phosphorylation process and

• interact with BCR-Abl-1 at the same binding site as IMT but show differences in the binding modes and with higher values of interaction energy. Compound 2c presented a MolDock value of −152.993 a.u. For compound 2d, the value was −152.127 a.u., and for compound 2g, it was −167.520 a.u. (Table 2

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

• relationships must be supported by ChIP-Seq evidence. Here, a nonlinear weighted sum called regulatory potential (RP) quantifies the strength of TF–gene interactions based on the proximity of TF binding site to the gene TSS and also the number of TF–gene binding interactions based experimentally detected ChIP

Chemical approaches to discover the full potential of peptide nucleic acids in biomedical applications

• Nikita Brodyagin,
• Martins Katkevics,
• Venubabu Kotikam,
• Christopher A. Ryan and
• Eriks Rozners

Beilstein J. Org. Chem. 2021, 17, 1641–1688, doi:10.3762/bjoc.17.116

Synthetic strategies of phosphonodepsipeptides

• Jiaxi Xu

Beilstein J. Org. Chem. 2021, 17, 461–484, doi:10.3762/bjoc.17.41

• -aminophosphonodichloride 92 with phenol and methyl (S)-2-hydroxypentanoate (18). All synthetic phosphonodepsipeptides 99, 102, and 104 were considered as glutathione-analogue phosphonopeptides as mechanism-based inhibitors of γ-glutamyl transpeptidase for probing the cysteinyl-glycine binding site (Scheme 16) [31

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

Multiswitchable photoacid–hydroxyflavylium–polyelectrolyte nano-assemblies

• Alexander Zika and
• Franziska Gröhn

Beilstein J. Org. Chem. 2021, 17, 166–185, doi:10.3762/bjoc.17.17

• transformation to the hydrolyzed form of the hydroxyflavylium molecule at state D leads to the removal of the positive charge and the addition of an extra binding site. Due to that, the ζ-potential increases while at the same time the effective surface charge density decreases followed by a destabilization of

• pH 7 (Figure 8), the data reveal that the first and third binding site are exothermic with ΔH1 = −4.3 kJ/mol and ΔH3 = −172.7 kJ/mol per polyelectrolyte binding site, respectively, which shows that strong ionic interactions and hydrogen bonding constitute these binding processes. Probably these

Insight into functionalized-macrocycles-guided supramolecular photocatalysis

• Minzan Zuo,
• Krishnasamy Velmurugan,
• Kaiya Wang,
• Xueqi Tian and
• Xiao-Yu Hu

Beilstein J. Org. Chem. 2021, 17, 139–155, doi:10.3762/bjoc.17.15

• quantum yield of 3.8 × 10−2 and 0.4, respectively. In contrast, for flavins without the zinc(II)–cyclen unit, only small amounts of product were observed, and the quantum yield was 30 times lower compared to that of the assembly with the flavin chromophore possessing a binding site. The mechanism may be

Supramolecular polymerization of sulfated dendritic peptide amphiphiles into multivalent L-selectin binders

• David Straßburger,
• Svenja Herziger,
• Katharina Huth,
• Moritz Urschbach,
• Rainer Haag and
• Pol Besenius

Beilstein J. Org. Chem. 2021, 17, 97–104, doi:10.3762/bjoc.17.10

• of multivalent interactions is the extracellular adhesion protein L-selectin. L-Selectin plays a critical role in inflammation processes by supporting the migration of leukocytes to inflammatory sites via adhesion to endothelial cells [19][20][21]. On a molecular level, a cationic binding site [22