Multivalent display of the antimicrobial peptides BP100 and BP143

• Imma Güell,
• Rafael Ferre,
• Kasper K. Sørensen,
• Esther Badosa,
• Iteng Ng-Choi,
• Emilio Montesinos,
• Eduard Bardají,
• Lidia Feliu,
• Knud J. Jensen and
• Marta Planas

Beilstein J. Org. Chem. 2012, 8, 2106–2117, doi:10.3762/bjoc.8.237

• active against human red blood cells pointing out that peptide preassembly is critical for the hemolytic activity. Notably, peptide preassembly resulted in an enhanced bactericidal effect. Keywords: antimicrobial activity; carbopeptides; multimeric structures; oxime ligation; phytopathogenic bacteria

• CH3CN and acetate buffer (0.1 M, pH 4.76) at room temperature for 2 h, but the expected carbopeptide 3 was not obtained. Since the use of aniline as nucleophilic catalyst for oxime ligation has been described to enhance reaction rates by up to three orders of magnitude [31][32][33], we assayed the

• formation of 3 using the previous CH3CN/acetate buffer solution but containing aniline (100 mM). Under these conditions we could not detect the carbopeptide 3 even when increasing the reaction time up to 48 h. Results were improved by lyophilizing the template prior to the oxime ligation. In this case, the

The Amadori rearrangement as glycoconjugation method: Synthesis of non-natural C-glycosyl type glycoconjugates

• Katharina Gallas,
• Gerit Pototschnig,
• Florian Adanitsch,
• Arnold E. Stütz and
• Tanja M. Wrodnigg

Beilstein J. Org. Chem. 2012, 8, 1619–1629, doi:10.3762/bjoc.8.185

• communication. In order to investigate and elucidate their many functions, reliable synthetic methods for the conjugation of carbohydrates to biomolecules are of crucial importance [2]. Several ligation strategies are described in the literature, such as chemical ligation [3], conjugation by means of click

• chemistry (Huisgen cycloaddition) [4][5], glycosylation protocols [6][7], and Staudinger ligation [8], just to mention the most prominent examples. However, many applications in this respect require a ligation method that is functional in aqueous medium, and, for economic purposes in general, protecting

• the repertoire of ligation methods, with the advantage that no protecting-group manipulations are necessary in the carbohydrate moiety and the reaction can be carried out in aqueous environment offering obvious advantages in glycobiology. In preliminary studies, several disaccharidic structures, such

Synthesis of trifunctional cyclo-β-tripeptide templates

• Frank Stein,
• Tahir Mehmood,
• Tilman Plass,
• Javid H. Zaidi and
• Ulf Diederichsen

Beilstein J. Org. Chem. 2012, 8, 1576–1583, doi:10.3762/bjoc.8.180

• containing an additional azide moiety, e.g., for ligation with click chemistry. Synthesis of cyclic peptides employing the oxidation-labile aryl hydrazide linker [11][24]. Functionalization of the cyclic β-tripeptide 4. Acknowledgements Financial support from the Deutsche Forschungsgemeinschaft (Research

Building photoswitchable 3,4'-AMPB peptides: Probing chemical ligation methods with reducible azobenzene thioesters

• Gehad Zeyat and
• Karola Rück-Braun

Beilstein J. Org. Chem. 2012, 8, 890–896, doi:10.3762/bjoc.8.101

• Gehad Zeyat Karola Ruck-Braun Institut für Chemie, Technische Universität Berlin, Strasse des 17. Juni 135, 10623 Berlin, Germany 10.3762/bjoc.8.101 Abstract Photoswitchable peptides were synthesized by using cysteine- and auxiliary-based native chemical ligation reactions. For this purpose, the

• two regioisomeric azobenzene building blocks 3,4'-AMPB thioester 1b and 4,4'-AMPB thioester 2b were employed in the ligation reactions. While 4,4'-AMPB requires the 4,5,6-trimethoxy-2-mercaptobenzyl auxiliary to minimize reduction of the diazene unit, 3,4'-AMPB can be used in combination with the

• 4,5,6-trimethoxy-2-mercaptobenzyl auxiliary as well as the Nα-2-mercaptoethyl auxiliary. Thus, 3,4'-AMPB derivatives/peptides proved to be significantly less prone to reduction by aliphatic and aromatic thiols than were the 4,4'-AMPB compounds. Keywords: acyl transfer auxiliary; azobenzenes; ligation

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

• -tuning of native chemical ligation (NCL), expressed protein ligation (EPL), and chemoenzymatic glycosylation techniques have all together enabled the synthesis of functional glycoproteins. The synthesis of structurally defined, complex glycopeptides or glyco-clusters presented on natural peptide

• of a MUC1 TN-glycopeptide, a polio peptide T-cell epitope and the Pam3CSK4 lipopeptide immune-stimulant was prepared by liposome-mediated native chemical ligation. Mice immunized with the three-component vaccine were injected with breast-cancer tumor cells, and were found to be significantly more

• synthetic glycoproteins. Since the discovery of native chemical ligation (NCL) by Kent and co-workers, numerous efforts have been made to prepare challenging protein targets [39][40][41][42][43][44]. In the NCL method, a native amide bond is formed by coupling of a C-terminal thioester with the N-terminal

2-Allylphenyl glycosides as complementary building blocks for oligosaccharide and glycoconjugate synthesis

• Hemali D. Premathilake and
• Alexei V. Demchenko

Beilstein J. Org. Chem. 2012, 8, 597–605, doi:10.3762/bjoc.8.66

• can be reverted as needed (active–latent strategy). Direct conjugation of the AP moiety to biomolecules, monolayers, arrays, etc., should be possible by executing thiol–ene chemistry [43], ozonolysis/reductive amination [44][45][46], or other ligation protocols [47][48]. Experimental General remarks

Synthesis of heteroglycoclusters by using orthogonal chemoselective ligations

• Baptiste Thomas,
• Michele Fiore,
• Isabelle Bossu,
• Pascal Dumy and
• Olivier Renaudet

Beilstein J. Org. Chem. 2012, 8, 421–427, doi:10.3762/bjoc.8.47

• combinations of carbohydrates. By using both oxime ligation and copper(I)-catalyzed alkyne–azide cycloaddition, two series of compounds bearing binary combinations of αMan, αFuc or βLac in an overall tetravalent presentation, and either 2:2 or 3:1 relative proportions, have been prepared. Keywords

• : chemoselective ligation; click chemistry; cyclopeptide; heteroglycocluster; oxime; Introduction Multivalent interactions between carbohydrates and proteins play key roles in diverse biological events, including fertilization, cell–cell communication, host–pathogen interactions, immune response and cancer

• methods, we decided to explore two chemoselective strategies to achieve this purpose. We first selected the oxime ligation since we have previously used this approach successfully for the preparation of sophisticated molecular systems, such as synthetic vaccines [27][28], immunomodulators [29], lectin

Biocatalytic hydroxylation of n-butane with in situ cofactor regeneration at low temperature and under normal pressure

• Svenja Staudt,
• Christina A. Müller,
• Jan Marienhagen,
• Christian Böing,
• Stefan Buchholz,
• Ulrich Schwaneberg and
• Harald Gröger

Beilstein J. Org. Chem. 2012, 8, 186–191, doi:10.3762/bjoc.8.20

• P450-monooxygenase BM-3, both the synthetic DNA and vector were cut for 1 h with 1 U each of FastDigest® endonucleases NcoI and MssI (Fermentas, St. Leon-Rot Germany) and purified by gel extraction (NucleoSpin® Gel Clean up, Macherey-Nagel, Düren, Germany). A ligation reaction was performed with the T4

• DNA Ligase (Fermentas, St. Leon-Rot Germany) according to the manufacturer’s instructions. The ligation reaction was subsequently transformed into chemically competent E. coli BL21 Gold (DE3) lacIQ1 cells [18], which were prepared by following a standard protocol [19]. For the chemically competent

Ratiometric fluorescent probe for enantioselective detection of D-cysteine in aqueous solution

• Xiao-bo Zhou,
• Wing-Hong Chan,
• Albert W. M. Lee and
• Chi-Chung Yeung

Beilstein J. Org. Chem. 2011, 7, 1508–1515, doi:10.3762/bjoc.7.176

• ratiometric fluorescent chemosensors for the detection of thiols have been constructed [29][30][31]. Recently, on the basis of a native chemical-ligation reaction, Lin and coworkers reported a FRET-based probe suitable for ratiometric imaging of cysteine in living cells [31]. Therefore, it is a challenging

The catalytic performance of Ru–NHC alkylidene complexes: PCy₃ versus pyridine as the dissociating ligand

• Stefan Krehl,
• Diana Geißler,
• Sylvia Hauke,
• Oliver Kunz,
• Lucia Staude and
• Bernd Schmidt

Beilstein J. Org. Chem. 2010, 6, 1188–1198, doi:10.3762/bjoc.6.136

• particular complex D, which became known as second generation Grubbs’ catalyst [16], and the Umicore M2 catalyst E [17][18]. The ligation of strongly σ-donating NHC’s leads to an improvement of catalytic activity, which sometimes equals the activity of Mo-based catalysts while maintaining the general

Design and synthesis of a cyclitol-derived scaffold with axial pyridyl appendages and its encapsulation of the silver(I) cation

• Pierre-Marc Léo,
• Christophe Morin and
• Christian Philouze

Beilstein J. Org. Chem. 2010, 6, 1022–1024, doi:10.3762/bjoc.6.115

• ligation of this scaffold. Results and Discussion Chemistry The synthesis of 1 was accomplished in 6 steps from the readily available myo-inositol orthobenzoate (2) [17] (Figure 2). As scyllo-inositol derivatives are derived from myo-inositols by an oxidation/reduction sequence [8][18][19], selective

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

• mannotrioside. Hence, a monomeric mannoside and the trisaccharide α-D-Man-(1→3)-[α-D-Man-(1→6)]-D-Man were selected as carbohydrate ligands and azidoethyl aglycone moieties were chosen to allow their ligation via an oligoglycine spacer of an appropriate length. The well-known squaric acid diester linkage

• glycopeptide 16. Boc-deprotection gave the required mannotrioside peptide 17 in the form of its TFA salt. The glycopeptides 8 and 17 were finally ligated via squaric acid employing DES for ligation (Scheme 3). Control of the pH-value during ligation allows sequential substitution [31]: the first amine reacts

• , the first ligation reaction was complete after 2 h. Then, mannoside 8 (20 mg, 32 µmol) and triethylamine (100 µL) were added and the basic reaction mixture was stirred at RT overnight. The solvent was removed under reduced pressure and the residue purified by GPC (Bio-Gel P4, water as eluent) to yield

Kinetic studies and predictions on the hydrolysis and aminolysis of esters of 2-S-phosphorylacetates

• Milena Trmčić and
• David R. W. Hodgson

Beilstein J. Org. Chem. 2010, 6, 732–741, doi:10.3762/bjoc.6.87

• )acetate. Use of 2-bromoacetic acid esters as heterobifunctional cross-linking agents. Cross-linking between thiophosphate 4, D-glucosamine (GlcNH2) and bromoacetyl-N-hydroxybenzotriazole 1 (R = Bt) or bromoacetyl-N-hydroxysuccinimide 1( R = NHS) in water/MeCN. Ligation of 2-bromoacetic acid esters 1 (R

Chemical aminoacylation of tRNAs with fluorinated amino acids for in vitro protein mutagenesis

• Shijie Ye,
• Allison Ann Berger,
• Dominique Petzold,
• Oliver Reimann,
• Benjamin Matt and
• Beate Koksch

Beilstein J. Org. Chem. 2010, 6, No. 40, doi:10.3762/bjoc.6.40

• -83855644 10.3762/bjoc.6.40 Abstract This article describes the chemical aminoacylation of the yeast phenylalanine suppressor tRNA with a series of amino acids bearing fluorinated side chains via the hybrid dinucleotide pdCpA and ligation to the corresponding truncated tRNA species. Aminoacyl-tRNAs can be

• molecule, direct chemical acylation is not possible. Hecht and co-workers developed a procedure in which Nα-protected amino acids were used to chemically aminoacylate the dinucleotide pCpA. Subsequent enzymatic ligation to truncated tRNAs (without the 3′-terminal CA dinucleotide) yielded the desired AA

• ]. Since the Nα-aminoacyl moiety is not stable under the ligation conditions, the Nα-amino group of amino acid was either protected beforehand as the 6-nitroverastryloxycarbonyl (NVOC) derivative, a moiety which can be removed photochemically after the ligation, or left unprotected. However, in both cases

Synthesis in the glycosciences

• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2010, 6, No. 16, doi:10.3762/bjoc.6.16

• strategy where the glycosidic linkage is substituted by another type of ligation, or where glycosidations are limited to rather simple reactions whilst complexity and multivalency of a complicated target structure are introduced by alternative methods. Examples of such a versatile approach are also

Synthetic incorporation of Nile Blue into DNA using 2′-deoxyriboside substitutes: Representative comparison of (R)- and (S)-aminopropanediol as an acyclic linker

• Daniel Lachmann,
• Sina Berndl,
• Otto S. Wolfbeis and
• Hans-Achim Wagenknecht

Beilstein J. Org. Chem. 2010, 6, No. 13, doi:10.3762/bjoc.6.13

• ]. Bioorthogonality is required for these ligation reactions in that both the functional group of the oligonucleotides and the functional group of the modifier should not be present in typical biomolecules and should react selectively with each other [11]. Over the last five years the Huisgen–Meldal–Sharpless “click

• ” ligation strategy has become an important strategy for postsynthetic labeling of DNA [12][13]. Huisgen described first the [2+3]-cycloaddition between alkynes and azides yielding 1,2,3-triazoles [14]. The utility of this reaction as a bioligation method has grown incredibly after Meldal [15] and – almost

• present in biopolymers and react selectively with each other in aqueous solutions. The “click” ligation can avoid the time-consuming synthesis of phosphoramidites as DNA building blocks which is especially important for brightly emitting fluorophores that are not compatible with the acidic, oxidative or

Versatile supramolecular reactivity of zinc-tetra(4-pyridyl)porphyrin in crystalline solids: Polymeric grids with zinc dichloride and hydrogen-bonded networks with mellitic acid

• Sophia Lipstman and
• Israel Goldberg

Beilstein J. Org. Chem. 2009, 5, No. 77, doi:10.3762/bjoc.5.77

• . Thus, the zinc ion in the porphyrin core can be four-coordinate (to the four pyrrole N-sites without any axial ligation and no option for self-coordination), or, as most frequently encountered, five-coordinate (binding, in addition, one axial ligand), or six-coordinate (in an octahedral environment

Synthesis of coumarin or ferrocene labeled nucleosides via Staudinger ligation

• Ivana Kosiova,
• Andrea Janicova and
• Pavol Kois

Beilstein J. Org. Chem. 2006, 2, No. 23, doi:10.1186/1860-5397-2-23

• gives iminophosphoranes which can react with almost any kind of electrophilic reagent, e.g. aldehydes/ketones to form imines or esters to form amides. This so-called Staudinger ligation has been employed in a wide range of applications as a general tool for bioconjugation including specific labeling of

• nucleic acids. Results A new approach for the preparation of labeled nucleosides via intermolecular Staudinger ligation is described. Reaction of azidonucleosides with triphenylphosphine lead to iminophosphorane intermediates, which react subsequently with derivatives of coumarin or ferrocene to form

• coumarin or ferrocene labeled nucleosides. Fluorescent properties of coumarin labeled nucleosides are determined. Conclusion New coumarin and ferrocene labeled nucleosides were prepared via intermolecular Staudinger ligation. This reaction joins the fluorescent coumarin and biospecific nucleoside to the