The preparation and properties of 1,1-difluorocyclopropane derivatives

• Kymbat S. Adekenova,
• Peter B. Wyatt and
• Sergazy M. Adekenov

Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25

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

• , during the catalytic process, the reactive guest should have a greater binding affinity or the photoproducts should have the lowest binding affinity with the supramolecular host to avoid product inhibition, so as to produce a better catalytic turnover efficiency [14][15]. However, it is quite complicated

• , the 1:1 (photoinert) and 2:2 (photoreactive) complexes (K1 = 33100 M−1 and K2 = 1480 M−1, respectively) could be formed, which have a stronger binding affinity than the native CD (K1 = 3800 M−1 and K2 = 150 M−1). Such interactions considerably enhance the population of the 2:2 complex (partially

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

• the effect of sulfate modification on the self-assembly properties of the dendritic peptide amphiphiles were performed using circular dichroism (CD) spectroscopy and electron transmission microscopy (TEM) as well as cryogenic TEM. Finally, the binding affinity of the sulfated supramolecular polymers

• [26]. These results show that the multivalent presentation of sulfate moieties on the surface of one-dimensional anisotropic supramolecular polymers noticeably enhances their affinity towards surface immobilized L-selectin. However, the binding affinity of the unmodified supramolecular polymer I was

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

• partner is subsequently passed over the immobilised protein, and the metal surface is irradiated at the same angle. If the partner protein binds with the immobilised one, a shift in the SPR angle occurs, indicating that PPIs have taken place, and the binding affinity, measured as the dissociation constant

• strength dependence is β-lactamase and its protein inhibitor BLIP, where binding decreases significantly as the salt concentration increases [53]. Chen et al. analysed the structural and thermodynamic data of 113 heterodimeric complexes and discussed the correlation between binding affinity and amount of

Selected peptide-based fluorescent probes for biological applications

• Debabrata Maity

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

• for AT-rich polynucleotides (log K = 4.6) than GC-rich polynucleotides (log K = 3.8). But probe 5 shows comparable binding affinity towards these two polynucleotides (log K = 4.7 and log K = 4.8, respectively, for p(dA·dT)2 and p(dG·dC)2). However, they both shows weaker affinity for dsRNA (polyA

Synthesis and investigation of quadruplex-DNA-binding, 9-O-substituted berberine derivatives

• Jonas Becher,
• Daria V. Berdnikova,
• Heiko Ihmels and
• Christopher Stremmel

Beilstein J. Org. Chem. 2020, 16, 2795–2806, doi:10.3762/bjoc.16.230

• derivatives. Notably, a clear relationship between the binding affinity of the ligands with the length of the alkyl linker chain, n, was not observed. However, depending on the structure, the ligands exhibited different effects when bound to the G4-DNA, such as fluorescent light-up effects and formation of

• not provide evidence for a significant effect of the adenine unit on the binding affinity of the ligands, for example, by additional association with the loops, presumably because the adenine residue is sterically shielded by the neighboring triazole unit. Keywords: berberine alkaloids; DNA ligands

• contributed significantly to the binding affinity depending on their spacing from the π-stacking unit. In the case of 4a–e, however, the position of the triazole and adenine unit relative to the berberine does not appear to be highly relevant for the overall binding affinity. It may be concluded that the

Selective recognition of ATP by multivalent nano-assemblies of bisimidazolium amphiphiles through “turn-on” fluorescence response

• Rakesh Biswas,
• Surya Ghosh,
• Shubhra Kanti Bhaumik and
• Supratim Banerjee

Beilstein J. Org. Chem. 2020, 16, 2728–2738, doi:10.3762/bjoc.16.223

• order to demonstrate the practical utility of the sensors, ATP binding studies were investigated in a highly competitive medium, i.e., a buffer containing 150 mM NaCl. In a medium of such a high ionic strength, the binding affinity typically gets diminished by electrostatic screening [72]. Although the

Water-soluble host–guest complexes between fullerenes and a sugar-functionalized tribenzotriquinacene assembling to microspheres

• Si-Yuan Liu,
• Xin-Rui Wang,
• Man-Ping Li,
• Wen-Rong Xu and
• Dietmar Kuck

Beilstein J. Org. Chem. 2020, 16, 2551–2561, doi:10.3762/bjoc.16.207

• Ka = (2.20 ± 0.16) × 105 M−1, respectively. The binding affinity between TBTQ-(OG)6 and C60 was further verified by Raman spectroscopy. The geometry of the complex of TBTQ-(OG)6 with C60 deduced from DFT calculations indicates that the driving force of the complexation is mainly due to 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

• equilibrium of the peptide towards conformations that are preorganized for antibody binding. This should decrease the overall entropic penalty upon binding, and therefore would explain an increased binding affinity for the glycosylated antigen. A cluster analysis showed that the dominant conformation for the

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

• phosphonate groups. While sulfonato-calix[4]arenes can bind unmodified Lys and Arg residues, their strength lies in the recognition and even tighter binding of methylated lysines [29]. Their binding affinity increases 70-fold from unmethylated over mono- and di- to trimethylated lysine, as every methyl group

• the free guests and both complexes. This study revealed that the binding affinity of cucurbit[7]uril to methylated lysines increases with increasing number of methyl groups (KMe3 > KMe2 > KMe > K). Ligand-detected 1H NMR for compound screening Ligand-detected 1H NMR methods have been well established

• residues on the protein surface, are also sensitive to pH and in some cases ionic strength and type of counter ions. It is important to keep in mind that these factors can also affect the binding affinity of a ligand. The pH affects the protonation state, and thus charge, of both the protein and charged

Naphthalene diimide–amino acid conjugates as novel fluorimetric and CD probes for differentiation between ds-DNA and ds-RNA

• Annike Weißenstein,
• Myroslav O. Vysotsky,
• Ivo Piantanida and
• Frank Würthner

Beilstein J. Org. Chem. 2020, 16, 2032–2045, doi:10.3762/bjoc.16.170

• strongly selective toward DNA [8]. The NDI 5 caused by far the strongest stabilisation – likely due to the three permanent charges. NDI 3b, with a longer and thus more flexible linker, has a higher ∆Tm value than the shorter and less adaptable NDI 3a. For an accurate determination of the binding affinity

Automated high-content imaging for cellular uptake, from the Schmuck cation to the latest cyclic oligochalcogenides

• Rémi Martinent,
• Javier López-Andarias,
• Dimitri Moreau,
• Yangyang Cheng,
• Naomi Sakai and
• Stefan Matile

Beilstein J. Org. Chem. 2020, 16, 2007–2016, doi:10.3762/bjoc.16.167

• intracellular delivery to a certain extent. In recent years, the development of artificial guanidinium systems with improved binding affinity and stability towards oxoanions has emerged as an important topic in this field [1][22][23][24]. In this context, Carsten Schmuck has created the 2-(guanidiniocarbonyl

• cations (6: KD = 20 mM, Figure 2). The amide NH unit in position 5 of the pyrrole ring is crucial for this binding affinity, which even exceeds the effect of the pyrrole NH moiety (4 and 5 vs 7: KD = 7.7 mM). In addition, the size and electronic structure of the pyrrole core are also important for this

• more stable complexes 12 with the phosphodiesters in the DNA backbone, and thus making it possible to transfect cells with shorter peptides. In 2015, the Schmuck group reported the first example of a small peptide with only four amino acids for gene transfection [27]. The binding affinity of 13 to DNA

Design, synthesis and application of carbazole macrocycles in anion sensors

• Alo Rüütel,
• Ville Yrjänä,
• Sandip A. Kadam,
• Indrek Saar,
• Mihkel Ilisson,
• Astrid Darnell,
• Kristjan Haav,
• Tõiv Haljasorg,
• Lauri Toom,
• Johan Bobacka and
• Ivo Leito

Beilstein J. Org. Chem. 2020, 16, 1901–1914, doi:10.3762/bjoc.16.157

• DMSO, we also studied binding using a higher water content in DMSO. The 10.0% m/m mixture was expected to lower the binding affinities for all receptor–anion combinations. The results are presented in Table 1 and Figure 6. Initially, the trend suggested a steady increase of the binding affinity with

• started to decrease. The initial increase of the binding affinity suggested that just fitting into the ring was not a sufficient criterion for predicting binding affinity. This was because for the macrocycles MC003–MC005, the computational geometries suggested that the ring is too small to bind any of the

Synthesis, docking study and biological evaluation of ᴅ-fructofuranosyl and ᴅ-tagatofuranosyl sulfones as potential inhibitors of the mycobacterial galactan synthesis targeting the galactofuranosyltransferase GlfT2

• Marek Baráth,
• Jana Jakubčinová,
• Zuzana Konyariková,
• Stanislav Kozmon,
• Katarína Mikušová and
• Maroš Bella

Beilstein J. Org. Chem. 2020, 16, 1853–1862, doi:10.3762/bjoc.16.152

• the acyclic tail of the native Galf is bound. The binding poses with the highest docking score of the four compounds with the highest predicted affinity are shown in Figure 2. The highest binding affinity was predicted for compounds 1bα, 2c, 3c and 1cβ. It can be seen that the compounds 2c, 3c and 1cβ

• Km or Ki values of the structures similar to the studied compounds were not available and therefore we were not able to create a more precise linear regression model for the binding affinity prediction. For this reason, we could use only a coarse correction for the calculated Ki values and the

• experimental Ki values can be expected in the mM and sub-mM range rather than in the µM and sub-µM range. However, the obtained predicted Ki values were reliable for the comparison of the fructofuranose and tagatofuranose compounds binding affinities with the UDP-Galf binding affinity. Moreover, the Ki values

Synthesis of new dihydroberberine and tetrahydroberberine analogues and evaluation of their antiproliferative activity on NCI-H1975 cells

• Giacomo Mari,
• Lucia De Crescentini,
• Serena Benedetti,
• Francesco Palma,
• Stefania Santeusanio and
• Fabio Mantellini

Beilstein J. Org. Chem. 2020, 16, 1606–1616, doi:10.3762/bjoc.16.133

• various inflammatory diseases. The main component of this rhizome is berberine (BER), an alkaloid with numerous pharmacological properties, which include anticancer and anti-inflammatory activities [1]. However, the low bioavailability, poor solubility, and moderate nucleic acid binding affinity

A dynamic combinatorial library for biomimetic recognition of dipeptides in water

• Florian Klepel and
• Bart Jan Ravoo

Beilstein J. Org. Chem. 2020, 16, 1588–1595, doi:10.3762/bjoc.16.131

• function yields a smaller increase in binding affinity than adding a second one, pointing towards a cooperative contribution of both phenyl rings. Pure F is the weakest tested binder, which hints at the selectivity towards dipeptides. Next we used NMR spectroscopy to further characterize the binding

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

• stability [5]. Also fluorinated aromatic amino acids can destabilize ΙΙ-cation interactions whereas their increased hydrophobicity enhances binding affinity [19]. Moreover, the incorporation of fluorinated amino acids into proteins provides the opportunity for probing structure (by NMR techniques) including

Cation-induced ring-opening and oxidation reaction of photoreluctant spirooxazine–quinolizinium conjugates

• Phil M. Pithan,
• Sören Steup and
• Heiko Ihmels

Beilstein J. Org. Chem. 2020, 16, 904–916, doi:10.3762/bjoc.16.82

• styrylquinolinizium unit at the neighboring carbon atom C5’’. At the same time, imine groups also have a high binding affinity to Cu2+ [83][84][85] and Fe3+ [86][87] so that we propose the initial coordination of the metal cation mainly to the imine nitrogen atom of the spirooxazine group in the course of the

Recent advances in Cu-catalyzed C(sp³)–Si and C(sp³)–B bond formation

• Balaram S. Takale,
• Ruchita R. Thakore,
• Elham Etemadi-Davan and
• Bruce H. Lipshutz

Beilstein J. Org. Chem. 2020, 16, 691–737, doi:10.3762/bjoc.16.67

• boron can lead to dative bond formation with enzymes, and therefore increase binding affinity. As shown in Scheme 1, several silicon [9][10][11][12] and boron-containing [13][14][15][16] drugs have already entered the market, or are currently in the drug development pipeline. As the number of drugs

Design and synthesis of diazine-based panobinostat analogues for HDAC8 inhibition

• Sivaraman Balasubramaniam,
• Sajith Vijayan,
• Liam V. Goldman,
• Xavier A. May,
• Kyra Dodson,
• Sweta Adhikari,
• Fatima Rivas,
• Davita L. Watkins and
• Shana V. Stoddard

Beilstein J. Org. Chem. 2020, 16, 628–637, doi:10.3762/bjoc.16.59

• the receptor using the Surflex-Dock Geom (SFXC) protocol [41][42][43] to evaluate the binding affinity of the ligand for the HDAC8 receptor. The C-scoring method was used to calculate these binding affinities and binding scores are given in −log10(Kd) values [45]. Docking simulations where ran

Photocontrolled DNA minor groove interactions of imidazole/pyrrole polyamides

• Sabrina Müller,
• Jannik Paulus,
• Jochen Mattay,
• Heiko Ihmels,
• Veronica I. Dodero and
• Norbert Sewald

Beilstein J. Org. Chem. 2020, 16, 60–70, doi:10.3762/bjoc.16.8

• % P1; 67% P2; after 1 d: 76% P3). Analysis of polyamide–DNA interaction by induced circular dichroism CD spectroscopic analysis is suitable for the characterization of DNA minor groove binders, providing semiquantitative information about binding affinity and thermal stability of the target dsDNA [47

• hyperchromicity of the signal on increasing PA concentration and the spectral behavior observed were characteristic for a B-DNA structure [51][53]. In contrast, Z-P2 did not reach saturation in the tested concentration range (Figure 3B), which is indicative of a lower binding affinity in comparison with the other

• saturation with the single-point mutation DNA D3’ at the tested concentration range, suggesting lower binding affinity compared to target dsDNA D3. The maxima of the ICD signals at 325 and 333 nm were plotted against the concentration of polyamide to quantify the binding of the PA to the cognate dsDNA. The

Photoreversible stretching of a BAPTA chelator marshalling Ca²⁺-binding in aqueous media

• Aurélien Ducrot,
• Arnaud Tron,
• Robin Bofinger,
• Ingrid Sanz Beguer,
• Jean-Luc Pozzo and
• Nathan D. McClenaghan

Beilstein J. Org. Chem. 2019, 15, 2801–2811, doi:10.3762/bjoc.15.273

• -withdrawing carbonyl function is generated from a secondary alcohol adjacent to the BAPTA binding site upon photoirradiation, which proved sufficient to lower the binding affinity 40-fold and liberate calcium in biological media [17]. This design was subsequently improved in a symmetrical variant and indeed a

• calcium sufficiently well and show sufficient photoactivity in this situation. However, the modest 2.5-fold difference of binding affinity between complexing and non-complexing forms, while comparable to the best-known photochromic variants [25][26], would need to be significantly increased (at least by

• switching in terms of quantum yields (0.08) and PSS composition (88% cis). The calcium binding affinity of the cis-form was diminished by circa 2.5-fold with respect to the trans-form as the chelator was stretched rendering the binding pocket ill-adapted to accommodate the calcium, as suggested by molecular

A chiral self-sorting photoresponsive coordination cage based on overcrowded alkenes

• Constantin Stuckhardt,
• Diederik Roke,
• Wojciech Danowski,
• Edwin Otten,
• Sander J. Wezenberg and
• Ben L. Feringa

Beilstein J. Org. Chem. 2019, 15, 2767–2773, doi:10.3762/bjoc.15.268

• considered to translate these geometrical changes to changes in properties such as guest binding affinity and selectivity. Schematic representation of a photoresponsive cage with ligands based on overcrowded alkenes. Aromatic region of stacked 1H NMR spectra (in CD3CN) of stable Z-1 and cage complex Pd2

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

• the binding affinity for the target protein [3][4][5] or the intrinsic functional activity (efficacy) [6][7]. Despite the considerable number of photoswitches reported to date, such as spiropyrans, diarylethenes, fulgides or azobenzenes, the most widely used moiety in the photopharmacology is the

• ligands [10]. The ensuing photochromic GPCR ligands are usually orthosteric and the photoswitching generally affects the functional potency [4][11][23] and/or the binding affinity [3][4][5][11] of the ligand (Figure 1A). However, as mentioned, GPCRs that endogenously bind large molecules (large peptides

• notably 4g deviate from this trend, since the percentage of cis-isomer in the PSS is significantly lower (58–80%). Trans-4a–i show a slight decrease in binding affinity compared to the subseries 2 and 3, amounting to low micromolar values (Table 2). Moreover, PSS affinity values are also modest, with only

In search of visible-light photoresponsive peptide nucleic acids (PNAs) for reversible control of DNA hybridization

• Lei Zhang,
• Greta Linden and
• Olalla Vázquez

Beilstein J. Org. Chem. 2019, 15, 2500–2508, doi:10.3762/bjoc.15.243

• , even at 90 °C. Both melting experiments and strand displacement assays demonstrated that mismatches had a dramatic effect on the binding affinity of the PNA, which was slightly compensated by the incorporation of oF4Azo. We observed modest, yet clear, differences in the formation of PNA/DNA duplexes