Potential of acylated peptides to target the influenza A virus

• Daniel Lauster,
• Damian Pawolski,
• Julian Storm,
• Kai Ludwig,
• Rudolf Volkmer,
• Henry Memczak,
• Andreas Herrmann and
• Sumati Bhatia

Beilstein J. Org. Chem. 2015, 11, 589–595, doi:10.3762/bjoc.11.65

• . Results and Discussion Peptide synthesis and characterization Peptide synthesis was performed using a rink amide resin on an automatic synthesizer by the Fmoc/tert-butyl strategy [17][18]. The N-terminus of the N-terminal free resin bound peptide was acylated with stearic acid using O-(benzotriazol-1-yl

Gold(I)-catalysed synthesis of a furan analogue of thiamine pyrophosphate

• Amjid Iqbal,
• El-Habib Sahraoui and
• Finian J. Leeper

Beilstein J. Org. Chem. 2014, 10, 2580–2585, doi:10.3762/bjoc.10.270

• , involving gold(I)-catalysed cyclisation of an alkynyl alcohol to form the furan ring. The furan analogue of thiamine diphosphate (ThDP) was also made and tested for binding to and inhibition of pyruvate decarboxylase (PDC) from Zymomonas mobilis (overexpressed in E. coli with a N-terminal His-tag). It is a

• in Escherichia coli has been used in such studies but, in order to simplify the purification, in this study the gene was cloned into a pET28a vector, to give the enzyme an N-terminal His6-tag. This form of the protein was overexpressed in high yield in E. coli, and was easily purified on a Ni2+-NTA

Synthesis of novel conjugates of a saccharide, amino acids, nucleobase and the evaluation of their cell compatibility

• Dan Yuan,
• Xuewen Du,
• Junfeng Shi,
• Ning Zhou,
• Abdulgader Ahmed Baoum and
• Bing Xu

Beilstein J. Org. Chem. 2014, 10, 2406–2413, doi:10.3762/bjoc.10.250

• article reports the synthesis of novel conjugates containing three fundamental biological build blocks (saccharide, amino acids, and nucleobase) and their cell compatibility. The attachment of the saccharide to the N-terminal of the peptide or the nucleobase to the C-terminal of the peptide apparently

Synthesis and optical properties of pyrrolidinyl peptide nucleic acid carrying a clicked Nile red label

• Nattawut Yotapan,
• Chayan Charoenpakdee,
• Pawinee Wathanathavorn,
• Boonsong Ditmangklo,
• Hans-Achim Wagenknecht and
• Tirayut Vilaivan

Beilstein J. Org. Chem. 2014, 10, 2166–2174, doi:10.3762/bjoc.10.224

• completion of the synthesis, the N-terminal Fmoc group was removed and the free amino group was capped by acetylation. The acpcPNA on the solid support was spilt to 0.5 µmol portions for a further labeling experiment and treated with 1:1 dioxane/aqueous NH3 at 60 °C overnight to remove the nucleobase- and

Multivalent scaffolds induce galectin-3 aggregation into nanoparticles

• Candace K. Goodman,
• Mark L. Wolfenden,
• Pratima Nangia-Makker,
• Anna K. Michel,
• Avraham Raz and
• Mary J. Cloninger

Beilstein J. Org. Chem. 2014, 10, 1570–1577, doi:10.3762/bjoc.10.162

• domain without the N-terminal domain, did not result in aggregate formation (see Table S3, Supporting Information File 1). No aggregates were observed for dendrimers 2–5 in solution without addition of galectin-3, and no aggregates were observed for galectin-3 when glycodendrimers were absent from the

• solution. Taken together, these data support aggregate initiation as a response to specific carbohydrate binding interactions between lectin and glycodendrimer. They also reveal the significance of the N-terminal domain in formation of higher order aggregates. The presence of these aggregates was confirmed

• ). The measured diameter of the CRD domain from the crystal structure of galectin-3 is roughly 3 nm [34]. The N-terminal domain consists of slightly fewer amino acids but is unstructured. Assuming the unstructured portion contributes about the same size or slightly more to the diameter of the protein as

Pyrene-modified PNAs: Stacking interactions and selective excimer emission in PNA₂DNA triplexes

• Alex Manicardi,
• Lucia Guidi,
• Alice Ghidini and
• Roberto Corradini

Beilstein J. Org. Chem. 2014, 10, 1495–1503, doi:10.3762/bjoc.10.154

• increased compared to the unmodified PNA7 (20 °C vs 10 °C). The presence of a second pyrene unit at N-terminal position is more stabilizing than that at C-term (compare PNA5 and PNA2, 4). PNA4 is characterized by a broad melting curve, whereas for PNA6 a continuous drift was observed already for the PNA

• result in destabilization of the overall structure (see Tm of PNA1 in Table 1). However, for PNA2, the combined effect of two pyrene pairs properly positioned allows to increase both stability and selectivity of PNA compared to unmodified one. The N-terminal pyrene unit, in addition to the central one

Design, automated synthesis and immunological evaluation of NOD2-ligand–antigen conjugates

• Marian M. J. H. P. Willems,
• Gijs G. Zom,
• Nico Meeuwenoord,
• Ferry A. Ossendorp,
• Herman S. Overkleeft,
• Gijsbert A. van der Marel,
• Jeroen D. C. Codée and
• Dmitri V. Filippov

Beilstein J. Org. Chem. 2014, 10, 1445–1453, doi:10.3762/bjoc.10.148

• were selected as target molecules (Figure 1). In conjugate 2 the carboxylic acid function of the isoglutamine of the MDP is linked to the N-terminal amine of the antigenic peptide. In conjugate 3 the same acid function of the MDP connects to the C-terminal lysine of the antigenic peptide. The 3

• the peptide (4 vs 5) does not seem to affect the NOD2 stimulating activity significantly, although the N-terminal conjugate appears slightly more active than the C-terminal conjugated MDP. The ability of conjugates 2–5 to induce DC maturation was evaluated by measuring interleukin 12 (IL-12p40

• ineffective as compared to the NOD2 transfected HEK cells. Conclusion We have described the assembly of two MDP building blocks, suitable for automated solid-phase peptide synthesis, and their application in the construction of a set of four MDP-peptide conjugates. These conjugates comprised a C- or N

Carbohydrate PEGylation, an approach to improve pharmacological potency

• M. Eugenia Giorgi,
• Rosalía Agusti and
• Rosa M. de Lederkremer

Beilstein J. Org. Chem. 2014, 10, 1433–1444, doi:10.3762/bjoc.10.147

• interaction with the target site. GlycoPEGylation of proteins PEGylation of proteins is usually performed on the ε-amine group of lysine or on the unprotected α-amino of the N-terminal amino acid using N-hydroxysuccinimidyl (NHS) activated PEGs or aldehyde PEGs. This conjugation leads to heterogeneous

Design and synthesis of multivalent neoglycoconjugates by click conjugations

• Feiqing Ding,
• Li Ji,
• Ronny William,
• Hua Chai and
• Xue-Wei Liu

Beilstein J. Org. Chem. 2014, 10, 1325–1332, doi:10.3762/bjoc.10.134

• ][27][28][29][30][31]. The α-GalNAc-linked glycopeptides, α-N-glycosidically linked to the polypeptide chain through the amido nitrogen of an asparagine residue at the N-terminal [32], were found to be the most important semi-synthetic glycoconjugates, usually modified from their naturally occurring

Automated solid-phase peptide synthesis to obtain therapeutic peptides

• Veronika Mäde,
• Sylvia Els-Heindl and
• Annette G. Beck-Sickinger

Beilstein J. Org. Chem. 2014, 10, 1197–1212, doi:10.3762/bjoc.10.118

• ]. The principle of peptide synthesis in homogenous solution is based on the reversible blocking of the carboxylic acid function of the C-terminal amino acid and the amino group of the N-terminal amino acid. In addition, activation of the free carboxy group of the N-terminal amino acid is necessary to

• coupling step, whereas the side-chain protecting groups and the resin ensure a permanent protection against unwanted side reactions [20]. Moreover, the relatively inert carboxy group has to be activated by a special auxiliary to increase the electrophilicity [23]. After loading of the resin, the N-terminal

• protecting group of the first amino acid can be removed and the next activated building block can be coupled. These alternating steps of Nα-deprotection, activation and coupling are repeated until the desired peptide chain is obtained. Following, the Nα-protecting group of the N-terminal amino acid has to be

Amino acid motifs in natural products: synthesis of O-acylated derivatives of (2S,3S)-3-hydroxyleucine

• Oliver Ries,
• Martin Büschleb,
• Markus Granitzka,
• Dietmar Stalke and
• Christian Ducho

Beilstein J. Org. Chem. 2014, 10, 1135–1142, doi:10.3762/bjoc.10.113

• . Within the context of our work regarding the total synthesis of muraymycin nucleoside antibiotics, we have developed a synthetic approach towards (2S,3S)-3-hydroxyleucine building blocks. Application of different protecting group patterns led to building blocks suitable for C- or N-terminal

Molecular architecture with carbohydrate functionalized β-peptides adopting 3₁₄-helical conformation

• Nitin J. Pawar,
• Navdeep S. Sidhu,
• George M. Sheldrick,
• Dilip D. Dhavale and
• Ulf Diederichsen

Beilstein J. Org. Chem. 2014, 10, 948–955, doi:10.3762/bjoc.10.93

• nucleophile preferentially attacks from the re-face as shown in TS 1 (Figure 4) to give 10b [48][55]. In the next step, ester saponification of 10a using lithium hydroxide afforded D-glucose derived β-amino acid 11a in 84% yield. Finally, N-terminal fluorenylmethoxycarbonyl (Fmoc) protection of the β-amino

Polyglycerol-functionalized nanodiamond as a platform for gene delivery: Derivatization, characterization, and hybridization with DNA

• Li Zhao,
• Yuki Nakae,
• Hongmei Qin,
• Tadamasa Ito,
• Takahide Kimura,
• Hideto Kojima,
• Lawrence Chan and
• Naoki Komatsu

Beilstein J. Org. Chem. 2014, 10, 707–713, doi:10.3762/bjoc.10.64

• Diamond Co., Ltd. (Lot. No. 66093). Glycidol was purchased from Kanto Chemical Co., Ltd. p-Toluenesulfonyl chloride and sodium azide were purchased from Nacalai Tesque, Co. Basic polypeptides binding propargyl glycine (G*) at an N terminal (G*BPP) were obtained from two sources; G*Lys8 and G*His8 were

Synthesis of (2S,3R)-3-amino-2-hydroxydecanoic acid and its enantiomer: a non-proteinogenic amino acid segment of the linear pentapeptide microginin

• Rajendra S. Rohokale and
• Dilip D. Dhavale

Beilstein J. Org. Chem. 2014, 10, 667–671, doi:10.3762/bjoc.10.59

• -hydroxy-β-aminodecanoic acid (AHDA, 2a) and its enantiomer 2b. The enantiomer of 2a is the N-terminal part of the natural linear pentapeptide microginin, which is used as an antihypertensive agent. Keywords: AHDA; carbohydrate; chiron approach; enantioselective; natural products; non-proteinogenic amino

• activity against angiotensin converting enzyme, which is responsible for the vasoconstriction of blood vessels [2][3][4]. Amongst different amino acids present in microginin, (2S,3R)-AHDA (2a) is a non-proteinogenic natural amino acid attached at the N-terminal part of the peptide chain. The α-hydroxy-β

Conformation of dehydropentapeptides containing four achiral amino acid residues – controlling the role of L-valine

• Michał Jewgiński,
• Joanna Krzciuk-Gula,
• Maciej Makowski,
• Rafał Latajka and
• Paweł Kafarski

Beilstein J. Org. Chem. 2014, 10, 660–666, doi:10.3762/bjoc.10.58

• type II, which is localized on the N-terminal part of the peptide. The values of the dihedral angles indicate that peptide 1 could display two types of a bent conformation in DMSO solution with an opposite orientation of turns (see Figure 2). As in the case of the peptide 1, our analysis of the

• torsion angles of the main chain of the obtained conformational cluster indicates that peptide 3 exhibits a right-handed helix [28]. Only such a bent structure with a flexible N-terminal part could explain the strong NOE signals between the methyl residue of the Boc group and the side chain of both the

• increase in solvent polarity promotes more ordered conformations of hexapeptides containing two dehydrophenylalanine residues [38]. On the other hand, Inai and co-workers showed that in the case of dehydropeptides containing only one chiral L-residue in the N-terminal position of the peptide a left-handed

Total synthesis and cytotoxicity of the marine natural product malevamide D and a photoreactive analog

• Werner Telle,
• Gerhard Kelter,
• Heinz-Herbert Fiebig,
• Peter G. Jones and
• Thomas Lindel

Beilstein J. Org. Chem. 2014, 10, 316–322, doi:10.3762/bjoc.10.29

• an identical ester section composed of dolaproine and (2S)-3-phenylpropan-1,2-diol. On the N-terminal side, the isopropyl and two sec-butyl side chains of isodolastatin H (2) are replaced by one sec-butyl and two isopropyl side chains, respectively, in the case of malevamide D (1). The total

• possible. The occurrence of conformers has been mentioned by Scheuer and co-workers and is also known for dolastatin 10 [12] and symplostatin 1 [13]. As an alternative route to the N-terminal tripeptide 11, we also investigated the coupling of the N-terminal dipeptide 15 with MMMAH tert-butyl ester (16

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2013, 9, 2265–2319, doi:10.3762/bjoc.9.265

New tridecapeptides of the theonellapeptolide family from the Indonesian sponge Theonella swinhoei

• Annamaria Sinisi,
• Barbara Calcinai,
• Carlo Cerrano,
• Henny A. Dien,
• Angela Zampella,
• Claudio D’Amore,
• Barbara Renga,
• Stefano Fiorucci and
• Orazio Taglialatela-Scafati

Beilstein J. Org. Chem. 2013, 9, 1643–1651, doi:10.3762/bjoc.9.188

• inferring the configurations of the two isoleucine residues. Similarly, it appeared reasonable to assume that, as in the co-occurring theonellapeptolide Id (and in all the theonellapeptolide found to date), the L-Val could be the N-terminal amino acid and thus, the D-Val should be the amino acid at

Recent progress in the discovery of small molecules for the treatment of amyotrophic lateral sclerosis (ALS)

• Allison S. Limpert,
• Margrith E. Mattmann and
• Nicholas D. P. Cosford

Beilstein J. Org. Chem. 2013, 9, 717–732, doi:10.3762/bjoc.9.82

• induce cellular stress through mitochondrial inhibition led to the formation of TDP-43 aggregates in the cytoplasm. The formation of TDP-43-containing cellular inclusions was dependent on the activation of stress-induced kinases such as c-Jun N-terminal kinase (JNK). Treatment of cells with bis

Synthesis and evaluation of cell-permeable biotinylated PU-H71 derivatives as tumor Hsp90 probes

• Tony Taldone,
• Anna Rodina,
• Erica M. DaGama Gomes,
• Matthew Riolo,
• Hardik J. Patel,
• Raul Alonso-Sabadell,
• Danuta Zatorska,
• Maulik R. Patel,
• Sarah Kishinevsky and
• Gabriela Chiosis

Beilstein J. Org. Chem. 2013, 9, 544–556, doi:10.3762/bjoc.9.60

• clinical trials, has been the ATP-competitive inhibitors that bind to the N-terminal nucleotide binding pocket [4][5]. Hsp90 belongs to the family of GHKL (G = DNA gyrase subunit B; H = Hsp90; K = histidine kinases; L = MutL) ATPases, which is distinguished by a unique bent shape of its nucleotide binding

• interest is the purine scaffold, including its representative PU-H71 (1a). This agent, currently in clinical investigation for cancer, binds to the N-terminal nucleotide binding pocket of Hsp90 [12]. We have shown that PU-H71 selects for tumor Hsp90 species, and therefore labeled derivatives of PU-H71 may

Thioester derivatives of the natural product psammaplin A as potent histone deacetylase inhibitors

• Matthias G. J. Baud,
• Thomas Leiser,
• Vanessa Petrucci,
• Mekala Gunaratnam,
• Stephen Neidle,
• Franz-Josef Meyer-Almes and
• Matthew J. Fuchter

Beilstein J. Org. Chem. 2013, 9, 81–88, doi:10.3762/bjoc.9.11

• epigenetic modifications, their biological outcomes, and how their misregulation is involved in diseases such as cancer [1][2]. The dynamic post-translational acetylation/deacetylation of histone proteins is one of the most commonly studied epigenetic events, and occurs at specific lysine residues on the N

• -terminal histone tails, which project out from the nucleosome (the fundamental repeating unit of chromatin). Acetylation/deacetylation of such lysine residues is achieved by the action of histone acetyltransferases (HATs) and histone deacetylases (HDACs), respectively. Histone deacetylation by HDACs causes

Asymmetric synthesis of γ-chloro-α,β-diamino- and β,γ-aziridino-α-aminoacylpyrrolidines and -piperidines via stereoselective Mannich-type additions of N-(diphenylmethylene)glycinamides across α-chloro-N-sulfinylimines

• Gert Callebaut,
• Sven Mangelinckx,
• Pieter Van der Veken,
• Karl W. Törnroos,
• Koen Augustyns and
• Norbert De Kimpe

Beilstein J. Org. Chem. 2012, 8, 2124–2131, doi:10.3762/bjoc.8.239

• specifically cleave off N-terminal dipeptides and are involved in the degradation of incretin hormones, including glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). GLP-1 is involved in the regulation of glucose homeostasis through stimulation of insulin secretion

The multicomponent approach to N-methyl peptides: total synthesis of antibacterial (–)-viridic acid and analogues

• Ricardo A. W. Neves Filho,
• Sebastian Stark,
• Bernhard Westermann and
• Ludger A. Wessjohann

Beilstein J. Org. Chem. 2012, 8, 2085–2090, doi:10.3762/bjoc.8.234

• synthesis of the N-terminal dipeptide 3, amino acid 9 was coupled with benzyl glycinate in the presence of ethyl chloroformate to give 10 in 88% yield. This intermediate was hydrogenated to afford the dipeptide acid 3 quantitatively. An alternative multicomponent approach to dipeptide 3 requires the use of

Chemical modification allows phallotoxins and amatoxins to be used as tools in cell biology

• Jan Anderl,
• Hartmut Echner and
• Heinz Faulstich

Beilstein J. Org. Chem. 2012, 8, 2072–2084, doi:10.3762/bjoc.8.233

• dimethylformamide. After cleavage of the N-terminal Fmoc group, the peptide was removed from the resin under simultaneous cleavage of the amino-side-chain protecting groups by incubation for 3 h in a mixture of trifluoroacetic acid (TFA) (12 mL), ethanedithiol (0.6 mL), anisole (0.3 mL), water (0.3 mL), and

Peptides presenting the binding site of human CD4 for the HIV-1 envelope glycoprotein gp120

• Julia Meier,
• Kristin Kassler,
• Heinrich Sticht and
• Jutta Eichler

Beilstein J. Org. Chem. 2012, 8, 1858–1866, doi:10.3762/bjoc.8.214

• compensation for the loss of R59 by R58. Finally, we probed the stereoselectivity of the peptide–gp120 interaction by replacing F43 in CD4-M5 by D-phenylalanine (CD4-M7). All peptides were equipped with an N-terminal hexahistidine tag for directed attachment to Ni-NTA assay plates. The tag, as well as the

• capping step using a mixture of acetic anhydride/pyridine/DMF (1:2:3; 30 min). The Fmoc group was removed by using 20% piperidine/DMF (20 min). After completing the sequence, the N-terminal amino group was acetylated. Peptides were cleaved from the resin by using Reagent K (TFA/water/phenol/thioanisole