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

Synthesis of a tubugi-1-toxin conjugate by a modulizable disulfide linker system with a neuropeptide Y analogue showing selectivity for hY1R-overexpressing tumor cells

• Rainer Kufka,
• Robert Rennert,
• Goran N. Kaluđerović,
• Lutz Weber,
• Wolfgang Richter and
• Ludger A. Wessjohann

Beilstein J. Org. Chem. 2019, 15, 96–105, doi:10.3762/bjoc.15.11

• well as a peptide–tubulysin A conjugate [K4(C(TubA)-βA-),F7,P34]-pNPY – representing a comparable PDC – compared to wildtype pNPY for their binding affinities at the NPY Y1 receptor subtype. While [F7,P34]-pNPY (IC50 = 1.3 nM) showed a comparable binding affinity as pNPY (IC50 = 1.8 nM), the Y1

New standards for collecting and fitting steady state kinetic data

• Kenneth A. Johnson

Beilstein J. Org. Chem. 2019, 15, 16–29, doi:10.3762/bjoc.15.2

• quantitative analysis, fulfilling the major goal of their work [1][2]. Estimating the binding affinity for the substrate as KS was an added bonus. These were profound discoveries that laid the foundation for enzymology throughout the 20th century. The Michaelis–Menten equation was originally derived assuming

• . Moreover, it shows that the Km value represents the balance point between the rate of turnover and the rate of substrate binding. The Km represents substrate binding affinity only in the special case of rapid equilibrium binding. A primary goal of fitting steady state data should be to accurately define

• binding affinity. The awkwardness is the result of historical precedent. Defining the specificity constant as kcat/Km carries with it the baggage of thinking of the specificity constant as a ratio rather than a single parameter. Logic is influenced by the words we use to describe observations. It actually

6’-Fluoro[4.3.0]bicyclo nucleic acid: synthesis, biophysical properties and molecular dynamics simulations

• Sibylle Frei,
• Andrei Istrate and
• Christian J. Leumann

Beilstein J. Org. Chem. 2018, 14, 3088–3097, doi:10.3762/bjoc.14.288

• polarizability of the modified nucleotide, and therefore influences the metabolic stability, the membrane permeability, the RNA- and protein-binding affinity of the AON [25][26][27][28][29]. Over the last almost two decades, fluorinated oligonucleotide analogs like 2’-deoxy-2’-fluoro-RNA (F-RNA) [26][30][31], 2

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

• (Figure 3) which displayed a >4-fold increase in its affinity for E. coli SC [63]. Recent evidence suggests that non-steroidal anti-inflammatory drugs (NSAIDs) have antimicrobial activity. Oakley et al. studied the E. coli β-clamp binding affinity of commercially available NSAIDs with the help of a FP

• phenylalanine benzyl ring, in which two chlorine atoms where incorporated in the benzene ring to achieve P14 (17, Figure 5) with a 15-fold increase of its binding affinity for the sliding clamp and reaching the 10−8 M range (IC50 = 0.077 μM) [65]. Recently, Løbner-Olesen and co-workers screened a library of

Pd-Catalyzed microwave-assisted synthesis of phosphonated 13α-estrones as potential OATP2B1, 17β-HSD1 and/or STS inhibitors

• Rebeka Jójárt,
• Szabolcs Pécsy,
• György Keglevich,
• Mihály Szécsi,
• Réka Rigó,
• Csilla Özvegy-Laczka,
• Gábor Kecskeméti and
• Erzsébet Mernyák

Beilstein J. Org. Chem. 2018, 14, 2838–2845, doi:10.3762/bjoc.14.262

• ]. Poirier et al. proved that 13α-derivatives of 3,17-estradiols have reduced binding affinity for estrogen receptor alpha and display no uterotropic activity [19]. The conformational change resulting from the inversion at C-13 leads to an epimer unable to bind to its nuclear receptors. We have recently

Novel solid-phase strategy for the synthesis of ligand-targeted fluorescent-labelled chelating peptide conjugates as a theranostic tool for cancer

• Sagnik Sengupta,
• Mena Asha Krishnan,
• Premansh Dudhe,
• Ramesh B. Reddy,
• Bishnubasu Giri,
• Sudeshna Chattopadhyay and
• Venkatesh Chelvam

Beilstein J. Org. Chem. 2018, 14, 2665–2679, doi:10.3762/bjoc.14.244

• of the intermediates. The various components that are assembled include the cell surface protein recognition ligand, a peptide spacer for enhanced solubility and binding affinity, a fluorescent tag for tissue staining and a chelating core to tether therapeutic cargos. This goal is smoothly achieved

• modified by removal of the L-glutamic acid residue to give the pteroic acid moiety (Figure 2). The binding affinity of the modified folate is relatively weaker than folic acid [41]. The targeting ligand, pteroic acid, is covalently coupled to 8-aminocaprylic acid to separate the active binding site of

• folate protein from the interference of fluorescent cargo attached to lysine and the chelating core as described for 13. Thus our newly designed bioconstructs 13 and 17 have the following four components, (i) a cell surface protein recognition ligand, (ii) a peptidic spacer which enhances the binding

Pathoblockers or antivirulence drugs as a new option for the treatment of bacterial infections

• Matthew B. Calvert,
• Varsha R. Jumde and
• Alexander Titz

Beilstein J. Org. Chem. 2018, 14, 2607–2617, doi:10.3762/bjoc.14.239

• compound was tested in a whole cell ELISA, it was shown that the apparent binding affinity increases by a factor of 250 versus methyl α-D-mannoside, while the valency only increased by a factor three. It should be noted that the full length FimH adhesin consists of two domains, a lectin and a pilin domain

Comparative cell biological study of in vitro antitumor and antimetastatic activity on melanoma cells of GnRH-III-containing conjugates modified with short-chain fatty acids

• Eszter Lajkó,
• Sarah Spring,
• Rózsa Hegedüs,
• Beáta Biri-Kovács,
• Sven Ingebrandt,
• Gábor Mező and
• László Kőhidai

Beilstein J. Org. Chem. 2018, 14, 2495–2509, doi:10.3762/bjoc.14.226

• (H-Lys(Dau=)-OH)) formed via lysosomal degradation of this type of conjugates had a lower binding affinity to DNA, than the free drug [35]. The two-fold higher intracellular fluorescence intensity of Dau was accompanied by almost two-fold higher cytotoxic activity compared to the conjugates. By

• than via intracellular mechanisms induced after the internalization of conjugates. Although the conjugates showed an opposite activity on melanoma adhesion (increasing effects) and chemotaxis (decreasing or neutral effects), based on our previous studies about the receptor binding affinity of

Rational design of boron-dipyrromethene (BODIPY) reporter dyes for cucurbit[7]uril

• Mohammad A. Alnajjar,
• Jürgen Bartelmeß,
• Robert Hein,
• Pichandi Ashokkumar,
• Mohamed Nilam,
• Werner M. Nau,
• Knut Rurack and
• Andreas Hennig

Beilstein J. Org. Chem. 2018, 14, 1961–1971, doi:10.3762/bjoc.14.171

• cyclohexylmethylammonium (cyH) cations by displacement titrations (see below) in our mixture of 30% (v/v) ACN/H2O, which gave Ka(Bnz) = 1.4 × 105 M−1 and Ka(cyH) = 1.5 × 107 M−1. This indicated that the binding affinity is lowered 100 to 1000-fold by reducing the hydrophobic effect in presence of 30% acetonitrile as also

Diazirine-functionalized mannosides for photoaffinity labeling: trouble with FimH

• Femke Beiroth,
• Tomas Koudelka,
• Thorsten Overath,
• Stefan D. Knight,
• Andreas Tholey and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2018, 14, 1890–1900, doi:10.3762/bjoc.14.163

• the following amino acid sequence: FACKTANGTAIPIGGGSANVYVNLAPVVNVGQNL-VVDLSTQIFCHNDYPETITDYVTLQRGSAYGGVLSNFSG-TVKYSGSSYPFPTTSETPRVVYNSRTDKPWPVALYLT-PVSSAGGVAIKAGSLIAVLILRQTNNYNSDDFQF-VWNIYANNDVVVPTGGHHHHHH. Docking studies Computer-aided docking studies were performed to evaluate the binding affinity

Synthesis of 9-arylalkynyl- and 9-aryl-substituted benzo[b]quinolizinium derivatives by Palladium-mediated cross-coupling reactions

• Siva Sankar Murthy Bandaru,
• Darinka Dzubiel,
• Heiko Ihmels,
• Mohebodin Karbasiyoun,
• Mohamed M. A. Mahmoud and
• Carola Schulzke

Beilstein J. Org. Chem. 2018, 14, 1871–1884, doi:10.3762/bjoc.14.161

• pH-sensitive light-up probe. Photometric and fluorimetric titrations of duplex and quadruplex DNA to 9-(arylethynyl)benzo[b]quinolizinium derivatives revealed a significant binding affinity of these compounds towards both DNA forms with binding constants of Kb = 0.2–2.2 × 105 M−1. Keywords: DNA

Synthesis of trifluoromethylated 2H-azirines through Togni reagent-mediated trifluoromethylation followed by PhIO-mediated azirination

• Jiyun Sun,
• Xiaohua Zhen,
• Huaibin Ge,
• Guangtao Zhang,
• Xuechan An and
• Yunfei Du

Beilstein J. Org. Chem. 2018, 14, 1452–1458, doi:10.3762/bjoc.14.123

• sciences. The introduction of this functional group in drug molecules can enhance their chemical and metabolic stability, improve their lipophilicity and bioavailability, and increase protein-binding affinity [1][2][3][4][5][6]. In this regard, the CF3 group has been introduced into many pharmaceutical

Novel unit B cryptophycin analogues as payloads for targeted therapy

• Eduard Figueras,
• Adina Borbély,
• Mohamed Ismail,
• Marcel Frese and
• Norbert Sewald

Beilstein J. Org. Chem. 2018, 14, 1281–1286, doi:10.3762/bjoc.14.109

• the vinca domain (Lys176, Val177 and Tyr210). Other than previously reported [52], the methoxy group of subunit B forms a hydrogen bond with Lys176 (Figure 2). Another binding mode of 2 with high binding affinity and hydrogen bond formation did not involve any interaction of subunit B, yet it was

• the other derivatives 23 and 24 (Figure 4). Besides hydrogen bond formation and binding affinity of inhibitors 2, 23 and 24, π-interactions and hydrophobic contacts with the binding pocket of the vinca domain were detected that would in turn increase the affinity of the inhibitor and its effect on the

Recyclable hypervalent-iodine-mediated solid-phase peptide synthesis and cyclic peptide synthesis

• Dan Liu,
• Ya-Li Guo,
• Jin Qu and
• Chi Zhang

Beilstein J. Org. Chem. 2018, 14, 1112–1119, doi:10.3762/bjoc.14.97

• . Compound 6 was subsequently oxidized with NaOCl/HCl to obtain FPID in 90% yield. Cyclic peptides, an important kind of peptides, possess several favorable properties such as target selectivity, good binding affinity and low toxicity, which make them attractive candidates in the development of therapeutics

An overview of recent advances in duplex DNA recognition by small molecules

• Sayantan Bhaduri,
• Nihar Ranjan and
• Dev P. Arya

Beilstein J. Org. Chem. 2018, 14, 1051–1086, doi:10.3762/bjoc.14.93

• as inhibitors of Werner and Bloom syndrome helicases and dual topoisomerase I/II inhibitors [37][38]. In order to improve DNA binding affinity and sequence specificity with reduced side effects, a series of synthetic hybrid molecules derived from distamycin and netropsin was synthesized and their

• affinity, sequence specificity, more cytotoxicity and minimizing the unwanted physiological side effects [43]. It has been observed that drugs with high degree of sequence specific binding affinity and selective alkylation of DNA could inhibit the binding of the regulatory proteins to DNA. Several

• fashion, they further reported a series of novel hybrids by tethering distamycin A with the antineoplastic agent uramustine via a flexible polymethylene chain of variable length (n = 1 to 6) in order to test their DNA binding affinity and cytotoxicity [57]. It has been observed that hybrid conjugates 8, 9

The first Pd-catalyzed Buchwald–Hartwig aminations at C-2 or C-4 in the estrone series

• Ildikó Bacsa,
• Dávid Szemerédi,
• János Wölfling,
• Gyula Schneider,
• Lilla Fekete and
• Erzsébet Mernyák

Beilstein J. Org. Chem. 2018, 14, 998–1003, doi:10.3762/bjoc.14.85

• -estradiol derivatives of 13α-estrone [23]. The 13-epimers were shown to exhibit no significant binding affinity for estrogen receptor alpha and display no uterotropic activity. Nevertheless, certain 13α-estrone derivatives possess important biological activities including antitumoral effect [24][25][26][27

• ]. Thus 13α-estrone is a suitable compound for the development of biologically active steroids lacking estrogenicity. Literature reveals that besides the inversion of C-13, the introduction of an amino group onto C-2 or C-4 of estrone also leads to significant decreases in its binding affinity for nuclear