Enzymatic synthesis of glycosides: from natural O- and N-glycosides to rare C- and S-glycosides

• Jihen Ati,
• Pierre Lafite and
• Richard Daniellou

Beilstein J. Org. Chem. 2017, 13, 1857–1865, doi:10.3762/bjoc.13.180

• sugar donor scope, and our group has shown the potency of this enzyme as a biocatalyst for the chemoenzymatic synthesis of non-natural desulfoglycosinolates [22]. More recently, S-glycosylated peptides have been identified, and characterized. In bacteria the structures of sublancin [23], glycocin F [24

Selective enzymatic esterification of lignin model compounds in the ball mill

• Ulla Weißbach,
• Saumya Dabral,
• Laure Konnert,
• Carsten Bolm and
• José G. Hernández

Beilstein J. Org. Chem. 2017, 13, 1788–1795, doi:10.3762/bjoc.13.173

• products or materials [2][3]. In organic chemistry, amino acids and short peptides are not only known for being stable under automated ball milling conditions during their preparation [4], but also when applied as catalysts to perform stereoselective transformations [5][6][7]. Encouraged by these facts, we

Mechanochemical enzymatic resolution of N-benzylated-β³-amino esters

• Mario Pérez-Venegas,
• Gloria Reyes-Rangel,
• Adrián Neri,
• Jaime Escalante and
• Eusebio Juaristi

Beilstein J. Org. Chem. 2017, 13, 1728–1734, doi:10.3762/bjoc.13.167

• resolution; mechanochemistry; Introduction β-Amino acids are rather interesting molecules that frequently exhibit exceptional biological properties [1][2][3]; for instance, some of them are efficient inhibitors of several enzymes [4][5]. Furthermore, β-amino acid residues can be used to protect peptides and

Chemical systems, chemical contiguity and the emergence of life

• Terrence P. Kee and
• Pierre-Alain Monnard

Beilstein J. Org. Chem. 2017, 13, 1551–1563, doi:10.3762/bjoc.13.155

• eutectic phase in water/ice [35][36][37], but computer modelling [38] and preliminary wet-chemistry experiments, which show a selective accumulation of long oligomers [39], already hint at the possibility of similar processes taking place in mineral formations. In the same environments, short peptides

• /association with the chemical system structure or to the encapsulation of a reaction “machinery” within it. Interface-linked catalysis: The oligomerization of peptides from amino acids with condensing agents has been demonstrated to occur in the presence of phospholipid vesicles [65][66][67]. In these studies

• ], the complexity of de novo RNA synthesis and its functional interconnection with other biopolymers in the cellular context question its early, single-handed role. The polymerization of short RNA chains and peptides has been investigated within aqueous vesicle lumens as well as water/oil emulsions, and

A new member of the fusaricidin family – structure elucidation and synthesis of fusaricidin E

• Marcel Reimann,
• Louis P. Sandjo,
• Luis Antelo,
• Eckhard Thines,
• Isabella Siepe and
• Till Opatz

Beilstein J. Org. Chem. 2017, 13, 1430–1438, doi:10.3762/bjoc.13.140

• 2,2-dimethylated pseudoproline (ΨMe,Me'Pro). This method has been reported to improve yields of macrolactamizations through stabilizing the cis-configuration of the amide bond and working as a turn inducer in peptides [17][18][19][20]. The ΨMe,Me'Pro unit turned out not to be completely stable during

• correct (see pages S38 and S39 of Supporting Information File 1). Conclusion In summary, two new members of the fusaricidin family, fusaricidins E and F, were isolated from fermentation broths of Paenibacillus sp. strain Lu16774 as an inseparable mixture of homologs. Structure elucidation of both peptides

An improved preparation of phorbol from croton oil

• Alberto Pagani,
• Simone Gaeta,
• Andrei I. Savchenko,
• Craig M. Williams and
• Giovanni Appendino

Beilstein J. Org. Chem. 2017, 13, 1361–1367, doi:10.3762/bjoc.13.133

• unclear. The use of THF was inspired by the work of Seebach on the solubility of peptides in ether-type organic solvents in the presence of certain alkaline cations [20], and it is not unconceivable that the interaction with sodium ions substantially diversifies the relative polarity of glycerol and

BODIPY-based fluorescent liposomes with sesquiterpene lactone trilobolide

• Ludmila Škorpilová,
• Silvie Rimpelová,
• Michal Jurášek,
• Miloš Buděšínský,
• Jana Lokajová,
• Roman Effenberg,
• Petr Slepička,
• Tomáš Ruml,
• Eva Kmoníčková,
• Pavel B. Drašar and
• Zdeněk Wimmer

Beilstein J. Org. Chem. 2017, 13, 1316–1324, doi:10.3762/bjoc.13.128

• . Specific drug targeting can be achieved by using, for example, antibodies, peptides, polyethylene glycol polymers, and last but not least, liposomes, which have been nowadays extensively investigated [1][2]. In general, liposomes are employed in order to enhance the therapeutic index of an applied drug by

Biomimetic molecular design tools that learn, evolve, and adapt

• David A Winkler

Beilstein J. Org. Chem. 2017, 13, 1288–1302, doi:10.3762/bjoc.13.125

• , and peptides and oligonucleotides can also be synthesized efficiently using automated methods, it is not yet possible to carry out chemical syntheses in a general sense using these technologies. However, several groups are making significant breakthroughs in generalizing and expanding the automated

Towards open-ended evolution in self-replicating molecular systems

• Herman Duim and
• Sijbren Otto

Beilstein J. Org. Chem. 2017, 13, 1189–1203, doi:10.3762/bjoc.13.118

• peptides and oligopeptides under prebiotic conditions. However, initially only very short peptides were produced in experiments under such conditions, raising doubts over their potential role as a precursor of life. When forming α-helices however, longer polypeptides can be stabilized by the formation of

• enhanced by electrostatic interactions between amino acids residing on the c and g positions of the α-helices. Ghadiri et al. showed that such coiled-coil peptides are capable of self-replication [35]. As depicted in Figure 7, helical polypeptides can act as a template for shorter peptide fragments by

• -replicating system involving peptides capable of diversification using a systems chemistry approach [52]. Following the discovery of an exponentially growing self-replicating system [53], we used two building blocks, 1 and 2, to form a dynamic combinational library (DCL) of self-replicating molecules. These

From chemical metabolism to life: the origin of the genetic coding process

• Antoine Danchin

Beilstein J. Org. Chem. 2017, 13, 1119–1135, doi:10.3762/bjoc.13.111

• summary, the most likely compounds that make the very first metabolic pathways are charged compounds with one to three carbon atoms, amino acids and a variety of peptides or related compounds, certainly not RNA [25]. Phosphates, with their remarkable metastable state in water were selected as surface

• (Figure 1). This created a collection of charged metabolites that would stick to surfaces and come in contact with each other, promoting a variety of reactions. The first stages of reproductive surface metabolism were prone to produce charged variants of peptides. Among the minerals that would carry over

• the first (iso)peptide-based metabolic pathways one finds iron–sulfur clusters (pyrite) [20] and polyphosphates [27]. Obviously, selected peptides would be part of the first prebiotic building blocks and compounds, exhibiting a range of promiscuous catalytic activities. This includes hydrolytic self

An eco-compatible strategy for the diversity-oriented synthesis of macrocycles exploiting carbohydrate-derived building blocks

• Sushil K. Maurya and
• Rohit Rana

Beilstein J. Org. Chem. 2017, 13, 1106–1118, doi:10.3762/bjoc.13.110

• ] glycosides and macrocyclic glycolipids [11]. Similarly, the copper-catalyzed azide–alkyne cycloaddition (CuAAC) reaction has found wide application in medicinal chemistry [33], biology [34][35], polymer chemistry [36], carbohydrates [37][38][39][40], peptides [41][42][43][44] and in materials science [45][46

G-Protein coupled receptors: answers from simulations

• Timothy Clark

Beilstein J. Org. Chem. 2017, 13, 1071–1078, doi:10.3762/bjoc.13.106

• , that the opsin/rhodopsin structures [15][16] used so-called high-affinity peptides to mimic the G-protein. It is likely that these proteins behave more like the native G-protein than the protein nanobodies. Review General GPCR structure Figure 2 shows a schematic diagram of the general structure of

Glyco-gold nanoparticles: synthesis and applications

• Federica Compostella,
• Olimpia Pitirollo,
• Alessandro Silvestri and
• Laura Polito

Beilstein J. Org. Chem. 2017, 13, 1008–1021, doi:10.3762/bjoc.13.100

• diameter range can be obtained [4]. Moreover, this synthetic procedure allows to introduce different types of carbohydrates and other ligands (i.e., polyethylene chains, lipids, peptides, DNA, RNA or fluorescent dyes) in controlled ratios [4]. A modification of this technique consists in the application of

Conformational study of L-methionine and L-cysteine derivatives through quantum chemical calculations and ³J_HH coupling constant analyses

• Weslley G. D. P. Silva,
• Carolyne B. Braga and
• Roberto Rittner

Beilstein J. Org. Chem. 2017, 13, 925–937, doi:10.3762/bjoc.13.94

• analysis; cysteine; methionine; NMR spectroscopy; quantum chemical calculations; Introduction Amino acids constitute the building blocks of proteins and peptides, which play an important role in numerous biological processes [1][2]. However, their studies in both isolated and condensed phases have been

• disulfide bonds formed by the oxidized thiol groups of cysteine confer exceptional stability for the peptides and proteins where they are present [10]. Thus, a systematic study on the conformational behavior of L-Met and L-Cys can reveal unique properties about the formation of proteins and peptides that

Chemoselective synthesis of diaryl disulfides via a visible light-mediated coupling of arenediazonium tetrafluoroborates and CS₂

• Jing Leng,
• Shi-Meng Wang and
• Hua-Li Qin

Beilstein J. Org. Chem. 2017, 13, 903–909, doi:10.3762/bjoc.13.91

• tetrafluoroborates; carbon disulfide; chemoselectivity; diaryl disulfides; photocatalyst; Findings The development of methods for the functionalization of peptides and proteins under mild conditions is a current frontier in the fields of chemistry, biology and drug discovery [1][2][3][4]. Most of the

Expression, purification and structural analysis of functional GABA transporter 1 using the baculovirus expression system

• Jing Hu,
• Chris Weise,
• Christoph Böttcher,
• Hua Fan and
• Jian Yin

Beilstein J. Org. Chem. 2017, 13, 874–882, doi:10.3762/bjoc.13.88

• , and tryptic peptides were analyzed either directly by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI–TOF MS) or guanidinated and then analyzed by MALDI. The labeled peptide peaks (Figure 2B) in the mass spectrum were identified as either GAT or GFP by matching the

• peptides from primary sequence databases with Mascot (http://www.matrixscience.com/). The biological function of recombinant proteins of mammalian origin expressed in insect cells may be altered by different N-glycan status. We observed that the terminal sialic acid residues are essential for the GABA

DMAP-assisted sulfonylation as an efficient step for the methylation of primary amine motifs on solid support

• Johnny N. Naoum,
• Koushik Chandra,
• Dorit Shemesh,
• R. Benny Gerber,
• Chaim Gilon and
• Mattan Hurevich

Beilstein J. Org. Chem. 2017, 13, 806–816, doi:10.3762/bjoc.13.81

• Methylated amines and amides are common motifs found in natural and synthetic compounds, e.g., small molecules, peptides, and oligonucleotides [1][2][3][4][5][6][7][8]. Methylation of amines and amides has found many applications in the fields of pharmacological research, materials science, and in synthetic

• peptides, proteins, and small molecules on solid support, in addition to other organic compounds in solution phase [22][24][25][27]. We found that the introduction of a single methyl group to an amine adjacent to a hindered moiety using the state-of-the-art strategies is extremely challenging (Figure 1A

• Supporting Information File 1). After completing the new procedure the methylated amine can be coupled with an amino acid to form a methylated amide. This procedure was, hence, suitable for the synthesis of peptides with multiple sites methylated amides. To further evaluate the efficiency of the new

Sulfamide chemistry applied to the functionalization of self-assembled monolayers on gold surfaces

• Loïc Pantaine,
• Vincent Humblot,
• Vincent Coeffard and
• Anne Vallée

Beilstein J. Org. Chem. 2017, 13, 648–658, doi:10.3762/bjoc.13.64

• applications in medicinal chemistry, sulfamide groups have been incorporated in self-assembling molecules [22][23][24][25][26][27], peptides [28], polymers [29], ligands [30], chiral auxiliaries [31][32][33] and in organocatalysts [34][35][36][37]. In light of the importance of the sulfamide functionality, our

Synthesis of 1-indanones with a broad range of biological activity

• Marika Turek,
• Dorota Szczęsna,
• Marek Koprowski and
• Piotr Bałczewski

Beilstein J. Org. Chem. 2017, 13, 451–494, doi:10.3762/bjoc.13.48

• -amino acid peptides with vasoconstrictor properties, produced primarily in the endothelium. They play a key role in vascular homeostasis and are responsible for proper vascular tone and vascular perfusion maintaining. In 2006, Miyaura et al. have synthesized selective endothelin A receptor antagonists

Biosynthetic origin of butyrolactol A, an antifungal polyketide produced by a marine-derived Streptomyces

• Enjuro Harunari,
• Hisayuki Komaki and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2017, 13, 441–450, doi:10.3762/bjoc.13.47

• diverse secondary metabolites with pharmaceutically useful bioactivities. Importantly, members of the genus Streptomyces have been the main source of drug discovery programs due to their high capacity in secondary metabolism including polyketides, peptides, terpenoids, alkaloids, and amino acid

Posttranslational isoprenylation of tryptophan in bacteria

• Masahiro Okada,
• Tomotoshi Sugita and
• Ikuro Abe

Beilstein J. Org. Chem. 2017, 13, 338–346, doi:10.3762/bjoc.13.37

• Masahiro Okada Tomotoshi Sugita Ikuro Abe Graduate School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan 10.3762/bjoc.13.37 Abstract Posttranslational isoprenylation is generally recognized as a universal modification of the cysteine residues in peptides and

• referred to as the farnesylation or geranylgeranylation of the thiol group of the C-terminal cysteine residue in peptides and proteins [4][5][6][7]. The isoprenylation of cysteine was first found in the peptide pheromones of basidiomycetous yeast [8][9][10]. Two peptide pheromones, tremerogen A-10 and

• processed, often with methyl esterification of the resulting C-terminal isoprenylcysteine. Considering the consensus sequence, a variety of organisms may produce isoprenylated peptides and proteins. Subsequently, numerous isoprenylated peptides and proteins, such as G-proteins including the human oncogene

Synthesis of acylhydrazino-peptomers, a new class of peptidomimetics, by consecutive Ugi and hydrazino-Ugi reactions

• Angélica de Fátima S. Barreto,
• Veronica Alves dos Santos and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2016, 12, 2865–2872, doi:10.3762/bjoc.12.285

• peptidomimetics with potential biological activity. Keywords: acylhydrazino-peptomers; consecutive Ugi reactions; peptide-peptoid hybrid; peptomer; Introduction In the last decades, increasing efforts have been extensively carried out to improve the pharmacological properties of natural peptides by structural

• modification of the amino acids [1][2][3][4][5][6][7][8]. These modifications allowed the obtention of molecules that mimic the properties of peptides (peptidomimetics) but usually exhibit greater proteolytic stability, increased cellular permeabilities and avoid stereochemical constraints. Figure 1 represents

• cancer therapeutics for being an antagonist of the vascular endothelial growth factor receptor 2 [13]; peptoid 2 is a ligand of the protooncogene Crk [14]; and peptoids 3 and 4 showed a high affinity for the α1-adrenergic and μ-specific opiate receptors [15], respectively (Figure 2). Unlike peptides, in

Biochemical and structural characterisation of the second oxidative crosslinking step during the biosynthesis of the glycopeptide antibiotic A47934

• Veronika Ulrich,
• Clara Brieke and
• Max J. Cryle

Beilstein J. Org. Chem. 2016, 12, 2849–2864, doi:10.3762/bjoc.12.284

• by OxyE, which acts between OxyB and OxyA in the cyclisation cascade [27]. In vivo experiments also hinted towards the activity of the Oxy enzymes against the substrate peptides whilst they remain bound to the NRPS [29], and in vitro experiments performed with OxyB from the vancomycin biosynthesis

• pathway confirmed that the Oxy enzymes do indeed act against peptides when these are bound to peptidyl carrier protein (PCP) domains [26]. More recently, it has been shown that the activity of the Oxy enzymes is actually reliant upon an additional conserved domain present within the final module of GPA

• teicoplanin system [13][16][17]. These results showed that OxyA, in contrast to OxyB, is highly selective for the correct stereochemistry of the peptide C-terminal residue and generally displays a higher selectivity for the structure of the substrate peptides [13][17]. Recent in vitro studies performed with

Chemical probes for competitive profiling of the quorum sensing signal synthase PqsD of Pseudomonas aeruginosa

• Michaela Prothiwa,
• Dávid Szamosvári,
• Sandra Glasmacher and
• Thomas Böttcher

Beilstein J. Org. Chem. 2016, 12, 2784–2792, doi:10.3762/bjoc.12.277

• additional mass corresponding to a probe modified cysteine residue Cys112 confirming that the CA probes indeed covalently labelled the active site cysteine. Only one peptide was detected with another cysteine residue (Cys138) modified by the probe compared to 64 detected peptides for CA2 labelled Cys112

• C112A mutant (PqsDm). B) Concentration dependence of labeling by the three active site directed probes. C) Mass spectrometric discovery of tryptic peptide fragments with probe CA2 attached to the active site Cys112 (No.: number of detected peptides). D) Competitive experiment with N-ethylmaleimide and

Interactions between cyclodextrins and cellular components: Towards greener medical applications?

• Loïc Leclercq

Beilstein J. Org. Chem. 2016, 12, 2644–2662, doi:10.3762/bjoc.12.261

• molecules into the lipid membrane leading to increase its fluidity. In contrast, at higher concentrations, the extraction of membrane constituents is ensured by micellar solubilization [84][85]. ii) Complexation of peptides and proteins and some applications Proteins are polymers of amino acids covalently

• and Pitha reported a study on the interaction of CDs with peptides containing aromatic amino acids [87]. From competitive spectrophotometry measurements, with p-nitrophenol as a competing reagent at pH 7.4, the authors determined the stability constants of aromatic amino acids and their oligopeptides

• of pentapeptides to α- and β-CD [88]. The two peptides used in this study were: Tyr-Ile-Gly-Ser-Arg (YIGSR) and Tyr-Gly-Gly-Phe-Leu (YGGFL). The former interacts specifically with the integrin receptors on specific neuronal cells whereas the latter is known to bind to brain receptor sites. From