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

1,2,3-Triazolium macrocycles in supramolecular chemistry

• Mastaneh Safarnejad Shad,
• Pulikkal Veettil Santhini and
• Wim Dehaen

Beilstein J. Org. Chem. 2019, 15, 2142–2155, doi:10.3762/bjoc.15.211

• association constant of macrocycle 3 in the more competitive 15% water/acetone medium, still demonstrating a high binding affinity for sulfate anion (Ka = 2.5 × 105 M−1) while the cage 3 did not show any binding toward the other tested anions in the more aqueous solvent mixture. 2.3. Redox-active 1,2,3

• to be very difficult to further proceed. However, the anion binding property of the corresponding bistriazolium macrocyclic part 5·(BF4)2 (Figure 5) has successfully been investigated using 1H NMR titration experiments in CD3CN. The highest binding affinity was found to be almost similar for both BzO

• an active metal template strategy. The 1H NMR binding data of 8·Se were studied in organic and aqueous solvent mixtures, revealing that ChB–anion binding affinity can compete with and even outperform hydrogen bonding receptor analogues. Due to the larger degree of covalency with the heavier halides

Archangelolide: A sesquiterpene lactone with immunobiological potential from Laserpitium archangelica

• Silvie Rimpelová,
• Michal Jurášek,
• Lucie Peterková,
• Jiří Bejček,
• Vojtěch Spiwok,
• Miloš Majdl,
• Michal Jirásko,
• Miloš Buděšínský,
• Juraj Harmatha,
• Eva Kmoníčková,
• Pavel Drašar and
• Tomáš Ruml

Beilstein J. Org. Chem. 2019, 15, 1933–1944, doi:10.3762/bjoc.15.189

• thapsigargin and its derivatives contributing to SERCA binding affinity (according to [22]): A) octanoyl, B) butanoyl or 2-methylbutanoyl, C) acetyl, D) angeloyl. Viability of rat peritoneal cells treated with archangelolide (1), dansylarchangelolide 5 and dansyl amide itself. Compounds were applied at 4 µM

Complexation of 2,6-helic[6]arene and its derivatives with 1,1′-dimethyl-4,4′-bipyridinium salts and protonated 4,4'-bipyridinium salts: an acid–base controllable complexation

• Jing Li,
• Qiang Shi,
• Ying Han and
• Chuan-Feng Chen

Beilstein J. Org. Chem. 2019, 15, 1795–1804, doi:10.3762/bjoc.15.173

• smaller than that of H1·G1, but much higher than that of H2·G1. In the case of H3 containing n-butoxy groups, almost no binding affinity toward G1 was observed under these conditions. Compared with G1, the protonated 4,4'-bipyridinium salt G3 showed similar complexation behavior but significantly lower

2,3-Dibutoxynaphthalene-based tetralactam macrocycles for recognizing precious metal chloride complexes

• Li-Li Wang,
• Yi-Kuan Tu,
• Huan Yao and
• Wei Jiang

Beilstein J. Org. Chem. 2019, 15, 1460–1467, doi:10.3762/bjoc.15.146

• rather wide guest scope. Therefore, we wondered whether multiple conformations would be observed by incorporating the 2,3-dialkoxynaphthalene units into tetralactam macrocycles as the sidewalls. How would this affect their binding affinity and selectivity of the resulting macrocycles? Herein, we describe

• isophthalamide bridging units bind these complexes with decent binding affinities. This macrocycle shows similar binding affinity to chloride, weaker affinity to the chloride complex of gold(III), and much stronger affinities to the chloride complexes of platinum(II) and palladium(II), when compared to the

• between the amide NH protons and the pyridine nitrogen atoms in 2, which pre-organizes the cavity for molecular recognition. How would this affect the binding affinity of 2? To answer this question, molecular modelling was performed. Only conformer I of 1 was used for the molecular modelling but both

Complexation of a guanidinium-modified calixarene with diverse dyes and investigation of the corresponding photophysical response

• Yu-Ying Wang,
• Yong Kong,
• Zhe Zheng,
• Wen-Chao Geng,
• Zi-Yi Zhao,
• Hongwei Sun and
• Dong-Sheng Guo

Beilstein J. Org. Chem. 2019, 15, 1394–1406, doi:10.3762/bjoc.15.139

• with carboxylated bipyridyl ligands (Ru(dcbpy)3), were screened as model guests on account of the desired strong host–guest binding affinity (Scheme 2). Fl, EY, RB, TPPS and AlPcS4 were employed as classical aggregation-caused quenching (ACQ) dyes; 2,6-TNS and 1,8-ANS were selected as intramolecular

• activation (BDA) [27]. In that work, we employed the four PSs and studied their host–guest complexation with GC5A. Each PS has a strong binding affinity upon 1:1 complexation with GC5A (Table 1), accompanied by a drastic annihilation of both fluorescence and photoactivity (reactive oxygen species generation

Bambusuril analogs based on alternating glycoluril and xylylene units

• Tomáš Lízal and
• Vladimír Šindelář

Beilstein J. Org. Chem. 2019, 15, 1268–1274, doi:10.3762/bjoc.15.124

• bind inorganic anions with high binding affinity and selectivity in both organic media and water [13][14]. Previously we used bambusurils to recognize and quantify anions in their complex mixtures at sub-micromolar concentrations by means of NMR [15]. However, sensing of anions by less expensive UV–vis

Diaminoterephthalate–α-lipoic acid conjugates with fluorinated residues

• Leon Buschbeck,
• Aleksandra Markovic,
• Gunther Wittstock and
• Jens Christoffers

Beilstein J. Org. Chem. 2019, 15, 981–991, doi:10.3762/bjoc.15.96

• , target compound 3 has the highest (0.57), target compound 7 the lowest (0.04) quantum yield. XPS characterization of SAMs. SAMs were prepared from compounds 3 and 7 exploiting the strong binding affinity of the ALA residue to gold surfaces [52]. The resulting layers of compound 3 (SAM 3) and 7 (SAM 7

Design of indole- and MCR-based macrocycles as p53-MDM2 antagonists

• Constantinos G. Neochoritis,
• Maryam Kazemi Miraki,
• Eman M. M. Abdelraheem,
• Ewa Surmiak,
• Tryfon Zarganes-Tzitzikas,
• Beata Łabuzek,
• Tad A. Holak and
• Alexander Dömling

Beilstein J. Org. Chem. 2019, 15, 513–520, doi:10.3762/bjoc.15.45

• size of 15–17 atoms and an oxygen as the heteroatom linker improves the binding affinity. All the active macrocycles have a 6-chloro-substituted indole core. It is well established that at the bottom of the Try23 pocket a hydrophobic small subpocket exists which is formed by Phe86, Ile103, Leu82 and

Study on the regioselectivity of the N-ethylation reaction of N-benzyl-4-oxo-1,4-dihydroquinoline-3-carboxamide

• Pedro N. Batalha,
• Luana da S. M. Forezi,
• Maria Clara R. Freitas,
• Nathalia M. de C. Tolentino,
• Ednilsom Orestes,
• José Walkimar de M. Carneiro,
• Fernanda da C. S. Boechat and
• Maria Cecília B. V. de Souza

Beilstein J. Org. Chem. 2019, 15, 388–400, doi:10.3762/bjoc.15.35

• eigenvalue in the Hessian second order matrix) [28][38][39][40][41]. Structures of some bioactive 4-oxoquinoline-3-carboxamide derivatives 1–4 with different bioactive profiles. Ki = binding affinity; AHA = acetohydroxamic acid (standard urease inhibitor); SAHA = suberoylanilide hydroxamic acid (an FDA