Unprecedented deoxygenation at C-7 of the ansamitocin core during mutasynthetic biotransformations

• Tobias Knobloch,
• Gerald Dräger,
• Wera Collisi,
• Florenz Sasse and
• Andreas Kirschning

Beilstein J. Org. Chem. 2012, 8, 861–869, doi:10.3762/bjoc.8.96

• to β-tubulin monomers at a site overlapping the vinca alkaloid binding site [9]. Recently, we disclosed several mutasynthetic studies aimed at the production of derivatives of ansamitocins 3–5 [10][11][12] as well as of geldanamycin (6), utilizing mutant strains of Actinosynnema pretiosum, the

High-affinity multivalent wheat germ agglutinin ligands by one-pot click reaction

• Henning S. G. Beckmann,
• Heiko M. Möller and
• Valentin Wittmann

Beilstein J. Org. Chem. 2012, 8, 819–826, doi:10.3762/bjoc.8.91

• of the triazole moieties as well as the central phenyl ring. This ring strain can be reduced by slightly pulling the GlcNAc residues directly attached to the linker out of the binding site, but at the expense of a less efficient multivalent binding of the two chitobiose entities. The chitobiose

• conformation. Ligand C2, and even more so ligand C3, possess very limited conformational freedom when adopting a chelating binding mode. Conformational changes within the linkers of C2 and C3 lead to forces that pull one or the other GlcNAc/chitobiose out of its binding site. This situation may increase the

• significantly increased conformational freedom. This is expected to facilitate binding in a chelating fashion at relatively low entropic costs. It is important to note that the third chitobiose unit of C6 cannot reach a third carbohydrate binding site of the WGA dimer. The closest distance to another binding

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

• on type 1 fimbriae is an attractive target for the inhibition of α-mannose-mediated cell adhesion [127][128][129][130][131]. Previous X-ray studies have proven that the FimH lectin has a monovalent binding site recognizing α-D-mannose [132][133]. In close proximity to the mannose-binding crevice, two

An easily accessible sulfated saccharide mimetic inhibits in vitro human tumor cell adhesion and angiogenesis of vascular endothelial cells

• Grazia Marano,
• Claas Gronewold,
• Martin Frank,
• Anette Merling,
• Christian Kliem,
• Sandra Sauer,
• Manfred Wiessler,
• Eva Frei and
• Reinhard Schwartz-Albiez

Beilstein J. Org. Chem. 2012, 8, 787–803, doi:10.3762/bjoc.8.89

• , revealed specific docking of GSF to the same binding site as the natural peptidic ligands of this integrin. The sulfate in the molecule coordinated with one manganese ion in the binding site. These studies show that this chemically easily accessible molecule GSF, synthesized in three steps from 3,4-bis

• -docking experiments using the cyclic peptide Cilengitide® (cyclo-[RGDfN(Me)V]) [27] as a ligand. The orientation of the pentapeptide Cilengitide and its binding to the binding site formed by the α and β chains of αvβ3 reproduced the published X-ray structure with high accuracy. The method thus validated

• was then used to dock GSF in silico to the same surface area. This resulted in two binding sites. One site was identical to the binding site described for the RGD motif [28] of the cyclic peptide and a second binding site was located inside the β-propeller domain of the αv domain (Figure 4A). This

Synthesis of fluorinated maltose derivatives for monitoring protein interaction by ¹⁹F NMR

• Michaela Braitsch,
• Hanspeter Kählig,
• Georg Kontaxis,
• Michael Fischer,
• Toshinari Kawada,
• Robert Konrat and
• Walther Schmid

Beilstein J. Org. Chem. 2012, 8, 448–455, doi:10.3762/bjoc.8.51

• eight α(1→4)-linked glucose (Glc) units with micromolar affinities [15][16]. X-ray structural data (PDB ID codes 1-DMB and 1ANF) demonstrated that the MBP (370 residues, Mr = 41 kDa) consists of two globular domains joined by a hinge-bending region, in which the ligand binding site is located in a cleft

• between the two domains. MBP exists in two different conformations: The ligand-free “open” form, exposing the binding site, and in the presence of a ligand, the “closed” form, trapping the ligand to provide contacts from both domains [17][18][19]. The number of protein–sugar hydrogen bonds associated with

Synthesis of multivalent host and guest molecules for the construction of multithreaded diamide pseudorotaxanes

• Nora L. Löw,
• Egor V. Dzyuba,
• Boris Brusilowskij,
• Lena Kaufmann,
• Elisa Franzmann,
• Wolfgang Maison,
• Emily Brandt,
• Daniel Aicher,
• Arno Wiehe and
• Christoph A. Schalley

Beilstein J. Org. Chem. 2012, 8, 234–245, doi:10.3762/bjoc.8.24

• amide coupling with 6 yielding binding site 2 in 73% yield. Since an excess of 7 was used and the 2’/6’-positions are sterically hindered, only monoiodination in the 4’-position was observed. This synthetic pathway thus gives reasonable overall yields. It should be mentioned that the diamide moiety

• polar aprotic solvent, such as acetone, acetonitrile, DMF or DMSO, which would solubilize the axles sufficiently well, would interfere strongly with pseudorotaxane formation. The tertiary amides are much more soluble and, therefore, appear to be the more appropriate binding site. However, the better

Fifty years of oxacalix[3]arenes: A review

• Kevin Cottet,
• Paula M. Marcos and
• Peter J. Cragg

Beilstein J. Org. Chem. 2012, 8, 201–226, doi:10.3762/bjoc.8.22

• conformations (cone and partial-cone), and a C3-symmetry [24]. This last feature can provide a suitable binding site for species that require trigonal-planar, tetrahedral or octahedral coordination environments. The flexibility of the macrocycles can allow them to establish ideal bond distances and angles to

• ) methylene groups had a binding affinity for linear primary alkyl ammonium ions from n-BuNH3+ to n-HexNH3+. 3.2 Upper-rim derivatives Although the lower rim has many advantages as a binding site for guests, not least in the relative ease with which substituents can be attached, the upper rim can also

Thermodynamic and kinetic stabilization of divanadate in the monovanadate/divanadate equilibrium using a Zn-cyclene derivative: Towards a simple ATP synthase model

• Hanno Sell,
• Anika Gehl,
• Frank D. Sönnichsen and
• Rainer Herges

Beilstein J. Org. Chem. 2012, 8, 81–89, doi:10.3762/bjoc.8.8

• artificial system driving endergonic condensations (Figure 1), we draw the conclusion that only one of the binding sites should provide metal coordination to the vanadate (or phosphate) and the other binding site should associate the nucleophilic anion by neutral hydrogen bonds. Similar effects obviously

Impact of the level of complexity in self-sorting: Fabrication of a supramolecular scalene triangle

• Kingsuk Mahata and
• Michael Schmittel

Beilstein J. Org. Chem. 2011, 7, 1555–1561, doi:10.3762/bjoc.7.183

• groups available for coordination in addition to its two bisimine nitrogens. Thus, unit 1 may either act as a strong bidentate, tridentate or tetradentate binding site for zinc(II) ions, and there is no large thermodynamic difference between a [Zn(16)(27)]+-type connection and a [Zn(16)(47)]+-type link

Effects of anion complexation on the photoreactivity of bisureido- and bisthioureido-substituted dibenzobarrelene derivatives

• Heiko Ihmels and
• Jia Luo

Beilstein J. Org. Chem. 2011, 7, 278–289, doi:10.3762/bjoc.7.37

• ], liquid crystals [18], chiral crystals [19][20][21][22][23], or cyclodextrins (CDs) [24][25][26] in such a way that the chiral environment within the binding site has an influence on preferential reaction pathways, thus inducing stereoselective photoreactions. Along these lines, the di-π-methane (DPM

Fluorometric recognition of both dihydrogen phosphate and iodide by a new flexible anthracene linked benzimidazolium-based receptor

• Kumaresh Ghosh and
• Debasis Kar

Beilstein J. Org. Chem. 2011, 7, 254–264, doi:10.3762/bjoc.7.34

• one binding site is present for interaction. Under similar experimental conditions, the emission of 2 was only slightly changed. Figure 8 displays the change in emission of 2 upon addition of 1 equiv of the same anions in CH3CN. In the presence of excess H2PO4− ions, the change in emission of 2 was

• less compared to the case of 1 (see Supporting Information File 1). The quenching of emission of 1 upon complexation is attributed to the activation of a PET process occurring between the binding site and the excited state of anthracene. The Stern–Volmer plot in Figure 9 illustrates the quenching

• ][42][43][44][45]. Iodide binding induced quenching of emission is attributed to the i) complementarity in size of iodide with the pseudocavity formed by the receptor-binding site and ii) heavy atom effect of iodide, which is also true for Br−. But the small quenching of emission in the presence of Br

An easy assembled fluorescent sensor for dicarboxylates and acidic amino acids

• Xiao-bo Zhou,
• Yuk-Wang Yip,
• Wing-Hong Chan and
• Albert W. M. Lee

Beilstein J. Org. Chem. 2011, 7, 75–81, doi:10.3762/bjoc.7.11

• guests, an additional binding site must be introduced. Thus, (S)-phenylalaninol (obtainable from L-phenylalanine) was reacted with isothiocyanate 4 to give sensor 2 in 40% yield. We envisaged that the additional alcohol functionality present in 2 could provide a binding site for the α-amino group of

Anthracene appended pyridinium amide–urea conjugate in selective fluorometric sensing of L-N-acetylvaline salt

• Kumaresh Ghosh,
• Tanmay Sarkar and
• Asoke P. Chattopadhyay

Beilstein J. Org. Chem. 2010, 6, 1211–1218, doi:10.3762/bjoc.6.139

• to the charge–charge interaction and formation of unconventional hydrogen bonds with the anionic guests [27]. In order to explore this binding site for a wide range of substrates, especially for amino acid derivatives, we report here the design and synthesis of a new fluororeceptor 1 where anthracene

• is attached to the binding site through a covalent CH2 spacer to yield a photo induced electron transfer sensory system [28]. The receptor 1 shows effective binding of the tetrabutylammonium salt of L-N-acetylvaline by exhibiting significant change in emission. Complexation induced formation of an

• observation [20]. The different modes of emission (enhancing and quenching) of 1 in the presence of the different guests studied is believed to be due to the structural difference and hydrogen bonding abilities of the guests for which the PET process occurring between the amide-urea binding site and the

Catalysis: transition-state molecular recognition?

• Ian H. Williams

Beilstein J. Org. Chem. 2010, 6, 1026–1034, doi:10.3762/bjoc.6.117

• concept. It is shown that reactant binding is intrinsically inhibitory, and that attempts to design catalysts that focus simply upon attractive interactions in a binding site may fail. Free-energy changes along the reaction coordinate for SN2 methyl transfer catalysed by the enzyme catechol-O-methyl

En route to photoaffinity labeling of the bacterial lectin FimH

• Thisbe K. Lindhorst,
• Michaela Märten,
• Andreas Fuchs and
• Stefan D. Knight

Beilstein J. Org. Chem. 2010, 6, 810–822, doi:10.3762/bjoc.6.91

• . It requires a photoactive ligand derivative, which can form a reactive species upon photo-excitation. Thus, incubation of the photoprobe with a protein followed by irradiation can result in a photo-crosslinked product, that provides structural information on the binding site of the protein (Figure 1

• just one monovalent carbohydrate binding site on the FimH protein [9][10][11][12][13]. Thus, we decided to employ photoactive ligands to probe carbohydrate binding to the known CRD in solution and to identify possibly auxiliary, so far unknown, binding sites on bacterial lectin FimH [2]. The known FimH

A bivalent glycopeptide to target two putative carbohydrate binding sites on FimH

• Thisbe K. Lindhorst,
• Kathrin Bruegge,
• Andreas Fuchs and
• Oliver Sperling

Beilstein J. Org. Chem. 2010, 6, 801–809, doi:10.3762/bjoc.6.90

• 1 fimbriae with a monovalent carbohydrate recognition domain (CRD) that is known from X-ray studies. However, binding studies with multivalent ligands have suggested an additional carbohydrate-binding site on this protein. In order to prove this hypothesis, a bivalent glycopeptide ligand with the

• and a pilin domain, which is required for fimbriae assembly [7]. The FimH adhesin domain features a carbohydrate binding site at its tip, called the carbohydrate recognition domain (CRD), which is known from X-ray studies [8][9][10][11]. It is a monovalent binding site, which can accommodate one α-D

• trisaccharide substructures, mainly α-D-Man-(1→3)-[α-D-Man-(1→6)]-D-Man. By employing site directed mutagenesis, it was found that mutations in one of these cavities significantly reduces binding, indicating that this could be a second carbohydrate binding site, relevant for ligand binding [21]. Thus, it was

RAFT polymers for protein recognition

• Alan F. Tominey,
• Julia Liese,
• Sun Wei,
• Klaus Kowski,
• Thomas Schrader and
• Arno Kraft

Beilstein J. Org. Chem. 2010, 6, No. 66, doi:10.3762/bjoc.6.66

• tetramethyl ester was subjected to LiBr-assisted nucleophilic cleavage to furnish the free bisphosphonate dianion binding site. This procedure has two major drawbacks. First, if the functional groups on the polymer backbone become restricted in their accessability, the final deprotection step will suffer from

Anthracene coupled adenine for the selective sensing of copper ions

• Kumaresh Ghosh and
• Tanushree Sen

Beilstein J. Org. Chem. 2010, 6, No. 44, doi:10.3762/bjoc.6.44

• sensor, shown in Figure 1. In both 1 and 2, adenine is defined as the binding site, which is connected to the anthracene probe via –CH2– spacer at the different regions of adenine. In order to find out the possible site for binding of metal ions, we optimized the geometries of both 1 and 2 at AM1 level

• compared to the cases of 1 and 2 with Cu2+. During the interaction process no other changes were observed. This finding thus indicates that the adenine moiety in both 1 and 2 acts as a metal ion binding site for which participation of anthracene in cation-π interaction is facilitated upon binding of metal

Molecular recognition of organic ammonium ions in solution using synthetic receptors

• Andreas Späth and
• Burkhard König

Beilstein J. Org. Chem. 2010, 6, No. 32, doi:10.3762/bjoc.6.32

• stoichiometry between a specific host and guest – or dynamic, where the binding of the first guest to the first binding site of a receptor affects the association constant of a second guest with a second binding site. Either positive allosteric binding – the first guest increases the association constant of the

• “key” in the complementary binding site or an inclusion compound. This host pre-organization leads to a major enhancement of the overall energy of guest complexation. The binding is energetically favored: Both enthalpic – a less solvent accessible area leads to a less strongly solvated guest with fewer

• has been attributed to the tetrahedral binding site geometry that favors complexation of the tetrahedral ammonium ion over that of the spherically symmetrical potassium ion, underlining the particular importance of hydrogen bonding and symmetry considerations in the design of ammonium ion recognition

Dipyridodiazepinone derivatives; synthesis and anti HIV-1 activity

• Nisachon Khunnawutmanotham,
• Nitirat Chimnoi,
• Arunee Thitithanyanont,
• Patchreenart Saparpakorn,
• Kiattawee Choowongkomon,
• Pornpan Pungpo,
• Supa Hannongbua and
• Supanna Techasakul

Beilstein J. Org. Chem. 2009, 5, No. 36, doi:10.3762/bjoc.5.36

• groups in 7 and 8 led to diminished activity relative to that of 5 and 6. 10 and 11, 8-amino analogues of nevirapine, were found to be ineffective inhibitors. Molecular docking To understand the binding mode of the new potent derivatives 5, 6 and 9 were docked into the HIV-1 RT binding site by using the

• program. The docked conformations of 5, 6, 9 and nevirapine are shown in Figure 3, and their GoldScores are presented in Table 2. In the wild-type and K103N binding sites, the docked orientations of 5, 6 and 9 are similar to that of nevirapine. In the Y181C binding site, except for 5, the orientations of

Synthesis and enzymatic evaluation of 2- and 4-aminothiazole- based inhibitors of neuronal nitric oxide synthase

• Graham R. Lawton,
• Haitao Ji,
• Pavel Martásek,
• Linda J. Roman and
• Richard B. Silverman

Beilstein J. Org. Chem. 2009, 5, No. 28, doi:10.3762/bjoc.5.28

• -groups at the 5-position of 4 should allow us to probe the hydrophobic binding pocket defined by P565, A566, V567, and F584 in the substrate binding site and optimize this interaction. Figure 2 shows the docking mode for 3 and 4a in rat nNOS. Initially, attempts were made to construct 3 and 4 using

Synthesis of rigidified flavin–guanidinium ion conjugates and investigation of their photocatalytic properties

• Harald Schmaderer,
• Mouchumi Bhuyan and
• Burkhard König

Beilstein J. Org. Chem. 2009, 5, No. 26, doi:10.3762/bjoc.5.26

• catalytic efficacy, flavin derivatives bearing a guanidinium ion as oxoanion binding site were prepared. Chromophore and substrate binding site are linked by a rigid Kemp’s acid structure. The molecular structure of the new flavins was confirmed by an X-ray structure analysis and their photocatalytic

• activity was investigated in benzyl ester cleavage, nitroarene reduction and a Diels–Alder reaction. The modified flavins photocatalyze the reactions, but the introduced substrate binding site does not enhance their performance. Keywords: flavin; guanidine; Kemp’s acid; photocatalysis; template

• flavin chromophore, the guanidinium substrate binding site and a Kemp’s acid derived rigid linker, starts from Kemp’s acid anhydride (5) [50][51][52]. The anhydride 5 was allowed to react with previously prepared flavins 4 and 8 [21] in the presence of DMAP as catalyst. The amide formation of the

The first salen- type ligands derived from 3',5'-diamino- 3',5'-dideoxythymidine and -dideoxyxylothymidine and their corresponding copper(II) complexes

• Daniel Koth,
• Michael Gottschaldt,
• Helmar Görls and
• Karolin Pohle

Beilstein J. Org. Chem. 2006, 2, No. 17, doi:10.1186/1860-5397-2-17

• binding site and the N-glycosidic bound thymine provides an additional chiral information and steric shielding. After the ligands had been added to a mixture of copper(II) acetate in THF the complexes were formed within a few minutes resulting in a dark green solution (Scheme 2). All four ligands 8–11

• 15 (384 nm). The complexes of the diastereomeric ligands could be obtained in a straightforward synthesis. They possess interesting features especially with regard to chiral catalysts or DNA strand formation. Although located off the metal ion the thymine base may act as a substrate binding site in

Colchitaxel, a coupled compound made from microtubule inhibitors colchicine and paclitaxel

• Karunananda Bombuwala,
• Thomas Kinstle,
• Vladimir Popik,
• Sonal O. Uppal,
• James B. Olesen,
• Jose Viña and
• Carol A. Heckman

Beilstein J. Org. Chem. 2006, 2, No. 13, doi:10.1186/1860-5397-2-13

• stacked on it in such a way that the nucleotide-binding site is embedded in the interface [8]. Ravelli and coworkers found colchicine binding site to be buried in the β subunit, boxed in by β-strands of the second domain and helices #7 and #8. The A ring of colchicine contacts residue 241[9], consistent

• binding. However, the acetamide linkage on ring B could be replaced by other alkyl amides with little change in potency [32]. Moreover, colchicine with an altered B ring still bound tubulin [33]. The binding site of paclitaxel is situated on the inner face of the polymerized microtubule, tucked into a

• bend formed by helix #6 and helix #7 near the + end of the microtubule and adjacent to strand #7. Here, the taxane may affect both the structure of the M loop and that of helix #6 which contacts the GTP binding site, so that it may both stabilize GTP against hydrolysis and stabilize the M loop against