Chemical structure metagenomics of microbial natural products: surveying nonribosomal peptides and beyond

• Thomas Ma and
• John Chu

Beilstein J. Org. Chem. 2024, 20, 3050–3060, doi:10.3762/bjoc.20.253

• the glycopeptide antibiotic family [62][63]. Their aromatic rings undergo oxidative coupling to form biaryl moieties that restrict atropisomerism; the resulting rigid structure is key to their high affinity binding to peptidoglycan intermediates [64][65]. Glycopeptide antibiotics include vancomycin

Palladium-catalyzed enantioselective three-component synthesis of α-arylglycine derivatives from glyoxylic acid, sulfonamides and aryltrifluoroborates

• Bastian Jakob,
• Nico Schneider,
• Luca Gengenbach and
• Georg Manolikakes

Beilstein J. Org. Chem. 2023, 19, 719–726, doi:10.3762/bjoc.19.52

• several well-known natural products with interesting biological properties, such as the glycopeptide antibiotics vancomycin and teicoplanin [5] or feglymycin [6], a 13mer peptide which contains nine α-arylglycines in its backbone. α-Arylglycine derivatives are used in the production of important drugs

Unsaturated fatty acids and a prenylated tryptophan derivative from a rare actinomycete of the genus Couchioplanes

• Shun Saito,
• Kanji Indo,
• Naoya Oku,
• Hisayuki Komaki,
• Masashi Kawasaki and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2021, 17, 2939–2949, doi:10.3762/bjoc.17.203

• Streptomyces, are especially noted, accounting for more than 800 metabolites of actinomycetes origin [11], which include the antiinfective aminoglycoside gentamicin [13], antidiabetic glycoside acarbose [14], glycopeptide antibiotic teicoplanin [15], enediyne antitumor component of drug-antibody conjugate

Semiautomated glycoproteomics data analysis workflow for maximized glycopeptide identification and reliable quantification

• Steffen Lippold,
• Arnoud H. de Ru,
• Jan Nouta,
• Peter A. van Veelen,
• Magnus Palmblad,
• Manfred Wuhrer and
• Noortje de Haan

Beilstein J. Org. Chem. 2020, 16, 3038–3051, doi:10.3762/bjoc.16.253

• complex, reflecting the high structural diversity of peptide and glycan portions. The use of glycopeptide-centered glycoproteomics by mass spectrometry is rapidly evolving in many research areas, leading to a demand in reliable data analysis tools. In recent years, several bioinformatic tools were

• developed to facilitate and improve both the identification and quantification of glycopeptides. Here, a selection of these tools was combined and evaluated with the aim of establishing a robust glycopeptide detection and quantification workflow targeting enriched glycoproteins. For this purpose, a tryptic

• digest from affinity-purified immunoglobulins G and A was analyzed on a nano-reversed-phase liquid chromatography–tandem mass spectrometry platform with a high-resolution mass analyzer and higher-energy collisional dissociation fragmentation. Initial glycopeptide identification based on MS/MS data was

Selected peptide-based fluorescent probes for biological applications

• Debabrata Maity

Beilstein J. Org. Chem. 2020, 16, 2971–2982, doi:10.3762/bjoc.16.247

• membrane-bound receptors interact strongly with short peptidic segments of a larger protein chain, for example, recognition of the RGD sequence (arginine–glycine–aspartic acid; Arg–Gly–Asp) by integrin receptors. They use noncovalent interactions including salt bridges [5]. Vancomycin, a glycopeptide

A consensus-based and readable extension of Linear Code for Reaction Rules (LiCoRR)

• Benjamin P. Kellman,
• Yujie Zhang,
• Emma Logomasini,
• Eric Meinhardt,
• Karla P. Godinez-Macias,
• Austin W. T. Chiang,
• James T. Sorrentino,
• Chenguang Liang,
• Bokan Bao,
• Yusen Zhou,
• Sachiko Akase,
• Isami Sogabe,
• Thukaa Kouka,
• Elizabeth A. Winzeler,
• Iain B. H. Wilson,
• Matthew P. Campbell,
• Sriram Neelamegham,
• Frederick J. Krambeck,
• Kiyoko F. Aoki-Kinoshita and
• Nathan E. Lewis

Beilstein J. Org. Chem. 2020, 16, 2645–2662, doi:10.3762/bjoc.16.215

• be reserved for other future uses. To specify a glycopeptide, users may also inscribe them directly in the peptide using the existing branching rules: “PEP(AG(LY)CAN)TIDE” would describe a biantennary glycan bound to the threonine of a peptide. Because the number sign is used to indicate a

• rule can be extended to glycopeptides providing a means of representing glycans directly embedded in a glycopeptide. “PEP(Gal[3S]b3(GNb6)AN)TIDE” would describe a trisaccharide O-glycan bound to the threonine of an eponymously named glycoprotein. Overall, the consensus in these representations centers

Comparative ligand structural analytics illustrated on variably glycosylated MUC1 antigen–antibody binding

• Christopher B. Barnett,
• Tharindu Senapathi and
• Kevin J. Naidoo

Beilstein J. Org. Chem. 2020, 16, 2540–2550, doi:10.3762/bjoc.16.206

• approach by investigating the in-silico binding of a peptide and glycopeptide epitope of the glycoprotein Mucin 1 (MUC1) binding with the antibody AR20.5. To study the binding, we performed molecular dynamics simulations using OpenMM and then used the Galaxy platform for data analysis. The same analysis

• analysis were carried out. These analyses were used to rapidly assess key features of the system, interrogate the dynamic structure of the ligand, and determine the role of glycosylation on the conformational equilibrium. The glycopeptide conformations in solution change relative to the peptide; thus a

• partially pre-structuring is seen prior to binding. Although the bound conformation of peptide and glycopeptide is similar, the glycopeptide fluctuates less and resides in specific conformers for more extended periods. This structural analysis which gives a high-level view of the features in the system

Computational tools for drawing, building and displaying carbohydrates: a visual guide

• Kanhaya Lal,
• Rafael Bermeo and
• Serge Perez

Beilstein J. Org. Chem. 2020, 16, 2448–2468, doi:10.3762/bjoc.16.199

• this tool ideal for integrated use with various glycoinformatics software and also for applications in glycoproteomics, glycomics and mass spectrometry (MS). One of the illustrations involves combined use with the gpAnnotate application, dedicated to score and annotate MS/MS glycopeptide spectrums in

GlypNirO: An automated workflow for quantitative N- and O-linked glycoproteomic data analysis

• Toan K. Phung,
• Cassandra L. Pegg and
• Benjamin L. Schulz

Beilstein J. Org. Chem. 2020, 16, 2127–2135, doi:10.3762/bjoc.16.180

• proteomic sample preparation and protease digestion, coupled with depletion of abundant proteins or enrichment of glycopeptides to enable their measurement. There have also been several advances in glycopeptide quantification strategies including chemical labelling, label-free and data-independent

• packages have been developed for analysis of outputs from MS technology to automate the process of transformation of raw MS data into ion intensities and matching them with appropriate glycan and peptide sequence databases for glycopeptide identification (reviewed in [12][13][14][15][16]). However, there

• are few efficient, robust, and automated workflows for glycopeptide quantification. There are several freely available software programs for quantitative label-free glycoproteomics using MS1 or data-dependent acquisition. These include LaCyTools [17], MassyTools [18], and GlycoSpectrumScan [19], which

A cyclopeptide and three oligomycin-class polyketides produced by an underexplored actinomycete of the genus Pseudosporangium

• Shun Saito,
• Kota Atsumi,
• Tao Zhou,
• Keisuke Fukaya,
• Daisuke Urabe,
• Naoya Oku,
• Md. Rokon Ul Karim,
• Hisayuki Komaki and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2020, 16, 1100–1110, doi:10.3762/bjoc.16.97

• metabolites; the biaryl bonding between Tyr and Trp is only precedented by kistamicin A, a vancomycin-class glycopeptide produced by an actinomycete of the genus Nonomuraea (family Streptosporangiaceae) [29][30] and TMC95A–D from an ascomycetous fungus Apiospora montagnei [31]; the (E)-2,3-dehydroadipyl

Synthesis of new asparagine-based glycopeptides for future scanning tunneling microscopy investigations

• Laura Sršan and
• Thomas Ziegler

Beilstein J. Org. Chem. 2020, 16, 888–894, doi:10.3762/bjoc.16.80

• Glycopeptides are generally found on virtually every eukaryotic and prokaryotic cell surface. So far, the study of glycopeptide interactions with other proteins gave some insight into important biological functions, for instance, intracellular communication, cell–cell recognition, immune response, and

• mechanisms of the interaction of glycopeptides with the cell surface [16]. Our focus lay on the preparation of glycopeptide libraries containing ʟ-asparagine since many saccharides on the cell surface are N-glycosidically linked to this amino acid [8]. The most abundant sugars found in these asparagine

• -linked structures are N-acetylglycosylamines, glucose, galactose, mannose, cellobiose, lactose, and maltose [19]. Therefore, we intended to prepare glycopeptide structures containing these sugars in a stepwise way, up to tripeptides. An orthogonal Fmoc/t-Bu protecting group strategy was chosen along with

Sugar-derived oxazolone pseudotetrapeptide as γ-turn inducer and anion-selective transporter

• Sachin S. Burade,
• Sushil V. Pawar,
• Tanmoy Saha,
• Navanath Kumbhar,
• Amol S. Kotmale,
• Manzoor Ahmad,
• Pinaki Talukdar and
• Dilip D. Dhavale

Beilstein J. Org. Chem. 2019, 15, 2419–2427, doi:10.3762/bjoc.15.234

• -Trp-Lys-Thy-OH) to get a glycopeptide which acts as an α-turn inducer [12]. Over the last several years, synthetic peptides are known to play a significant role in the design of artificial ion transport systems [13][14][15][16]. Recently, our group has synthesized fluorinated acyclic and cyclic

Design, synthesis and biological evaluation of immunostimulating mannosylated desmuramyl peptides

• Rosana Ribić,
• Ranko Stojković,
• Lidija Milković,
• Mariastefania Antica,
• Marko Cigler and
• Srđanka Tomić

Beilstein J. Org. Chem. 2019, 15, 1805–1814, doi:10.3762/bjoc.15.174

• stimulation of the immune response in this class of adjuvants. Similarly, N-glycolyl muramyl peptides obtained by the oxidation of the N-acetyl group of MDP induce significantly a higher activation of NOD2 than MDP [29][30]. Glycopeptide 21 was identified as the most potent adjuvant in this experiment and in

Synthesis and conformational preferences of short analogues of antifreeze glycopeptides (AFGP)

• Małgorzata Urbańczyk,
• Michał Jewgiński,
• Joanna Krzciuk-Gula,
• Jerzy Góra,
• Rafał Latajka and
• Norbert Sewald

Beilstein J. Org. Chem. 2019, 15, 1581–1591, doi:10.3762/bjoc.15.162

• populated clusters. The biggest cluster has been found for clustering based on the φ, ψ torsion angles of Ala2-Thr3-Ala4. The biggest cluster contained more than 64% of all structures (see Table 4). Therefore, such observation can suggest high stability of the central part of the investigated glycopeptide

• (see Table 3) allowed only to conclude that peptide 4 did not adopt the often observed polyproline type helix [38] nor the extended conformation postulated by Corzana et al. [33]. Interestingly, also the arrangement of the monosaccharide moiety is much more ordered in glycopeptide 4 in comparison to

• of monosaccharide moiety. A) cluster 1 for glycopeptide 3, B) cluster 1 for glycopeptide 4. A) Modification of Fmoc-Sieber-PS resin: a. piperidine in DMF (20% v/v), rt; 3 × 10 min; b. o-NBS-Cl (4 equiv), collidine (10 equiv) NMP, rt, 2 h, twice; c. triphenylphosphine (PPh3, 5 equiv), methanol (MeOH

Solid-phase synthesis of biaryl bicyclic peptides containing a 3-aryltyrosine or a 4-arylphenylalanine moiety

• Iteng Ng-Choi,
• Àngel Oliveras,
• Lidia Feliu and
• Marta Planas

Beilstein J. Org. Chem. 2019, 15, 761–768, doi:10.3762/bjoc.15.72

• amino acids [11]. Cyclic peptides containing biaryl linkages constitute attractive targets. On the one hand, a wide range of biaryl natural products have been reported to display interesting biological properties, such as biphenomycins, arylomycins and glycopeptide antibiotics [4]. On the other hand

Unexpected loss of stereoselectivity in glycosylation reactions during the synthesis of chondroitin sulfate oligosaccharides

• Teresa Mena-Barragán,
• José L. de Paz and
• Pedro M. Nieto

Beilstein J. Org. Chem. 2019, 15, 137–144, doi:10.3762/bjoc.15.14

• oligosaccharides in order to improve the glycosylation efficiency [20][21]. In this approach, glucose instead of GlcA residues were employed in the oligosaccharide assembly and final oxidation and derivatization was carried out at the oligomer stage. Syndecan-1 glycopeptide containing a CS type A sequence was also

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

• sequence of LecB differs among clinical isolates of this highly variable pathogen, with some mutations in close proximity to the carbohydrate binding site, but carbohydrate-binding function is preserved across all lectins investigated [42][43]. The glycopeptide dendrimer 13 (Figure 3) showed potent

Nanoreactors for green catalysis

• M. Teresa De Martino,
• Loai K. E. A. Abdelmohsen,
• Floris P. J. T. Rutjes and
• Jan C. M. van Hest

Beilstein J. Org. Chem. 2018, 14, 716–733, doi:10.3762/bjoc.14.61

• (X = I or Br) in water [100]. Other examples of water-soluble dendrimers are peptide- and glycol-based dendrimers [102][103]. As a result of their compositional versatility, they have been reported in many applications for biomedical engineering (e.g., glycopeptide dendrimers for drug delivery [104

Synthetic and semi-synthetic approaches to unprotected N-glycan oxazolines

• Antony J. Fairbanks

Beilstein J. Org. Chem. 2018, 14, 416–429, doi:10.3762/bjoc.14.30

• contains a glycopeptide, often termed sialylglycopeptide (SGP), which is comprised of a short peptide linked to a complex biantennary N-glycan. Thus egg yolks can serve as a source of this complex biantennary N-glycan [(NeuAcGalGlcNAcMan)2ManGlcNAc2], following isolation of SGP, and subsequent enzymatic

The use of 4,4,4-trifluorothreonine to stabilize extended peptide structures and mimic β-strands

• Yaochun Xu,
• Isabelle Correia,
• Tap Ha-Duong,
• Nadjib Kihal,
• Jean-Louis Soulier,
• Julia Kaffy,
• Benoît Crousse,
• Olivier Lequin and
• Sandrine Ongeri

Beilstein J. Org. Chem. 2017, 13, 2842–2853, doi:10.3762/bjoc.13.276

• residue, acting as a β-sheet breaker element and thus preventing the interactions between Aβ species [15]. The introduction of such fluorinated peptides in larger structures, such as glycopeptide or β-hairpin compounds can be envisaged. Indeed we have previously demonstrated that small peptides

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

• cytotoxic activity toward lymphoma cells, resulting active at a very low micromolar range [101]. With the aim to activate the human immune system against self-tumor cells, Schlecht and co-workers designed the synthesis of AuNPs functionalized with Mucin1(MUC1)-glycopeptide antigens [102]. Mucins are a

• -glycopeptide antigens were able to stimulate the immune system, suggesting GAuNPs are interesting platforms for developing new immunotherapeutics. The potential of AuNPs as antigen carriers for the development of synthetic vaccines is still being investigated in the context of bacterial infections. NPs are

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

• Biochemistry and Molecular Biology and ARC Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, Victoria 3800, Australia 10.3762/bjoc.12.284 Abstract The chemical complexity and biological activity of the glycopeptide antibiotics (GPAs) stems from their unique crosslinked structure

• homologues can display significantly different catalytic propensities despite their overall similarities. Keywords: crystal structure; cytochrome P450; glycopeptide antibiotic; peptide; phenolic coupling; Introduction The glycopeptide antibiotics (GPAs) are a series of highly modified heptapeptide natural

• enables them to bind to the dipeptide terminus of the peptidoglycan precursor lipid II [1][2]. This three-dimensional structure is generated by the high degree of crosslinking exhibited by the glycopeptide antibiotics: in the case of the two most widely known natural examples (vancomycin and teicoplanin

Synthesis and NMR studies of malonyl-linked glycoconjugates of N-(2-aminoethyl)glycine. Building blocks for the construction of combinatorial glycopeptide libraries

• Markus Nörrlinger,
• Sven Hafner and
• Thomas Ziegler

Beilstein J. Org. Chem. 2016, 12, 1939–1948, doi:10.3762/bjoc.12.183

• Markus Norrlinger Sven Hafner Thomas Ziegler Institute of Organic Chemistry, University of Tuebingen, Auf der Morgenstelle 18, 72076 Tuebingen, Germany 10.3762/bjoc.12.183 Abstract Four glycoconjugate building blocks for the construction of combinatorial PNA like glycopeptide libraries were

• ligand are highly desirable [10][11][12][13]. In our previous work we introduced various trifunctional glycopeptide building blocks derived from aspartic acid, 3-aminomethyl-5-aminobenzoic acid [14] and from the PNA-like N-(2-aminoethyl)glycine (AEG) backbone to which sugar moieties were linked through

• to generate glycopeptide libraries of more complex nature by automated SPOT synthesis. cis- and trans rotamer of protected PNA building blocks 1a–d and 2a–d. cis- and trans rotamer of unprotected PNA-building block 3. Rotameric structures of dimeric PNA glycoconjugate 4. 1H NMR (400 MHz) of building

Synthesis and biological evaluation of a novel MUC1 glycopeptide conjugate vaccine candidate comprising a 4’-deoxy-4’-fluoro-Thomsen–Friedenreich epitope

• Manuel Johannes,
• Maximilian Reindl,
• Bastian Gerlitzki,
• Edgar Schmitt and
• Anja Hoffmann-Röder

Beilstein J. Org. Chem. 2015, 11, 155–161, doi:10.3762/bjoc.11.15

• to rapid in vivo degradation. To overcome these drawbacks, novel fluorinated MUC1 glycopeptide-BSA/TTox conjugate vaccines have been prepared. Immunization of mice with the 4’F-TF-MUC1-TTox conjugate resulted in strong immune responses overriding the natural tolerance against MUC1 and producing

• to serve as effective C–OH mimics and the absence of fluorine in most organisms [43]. For instance, a MUC1 glycopeptide–tetanus toxoid conjugate (MUC1–TTox) containing a difluorinated 6,6’-F2-TF analog inducing a strong immune response in mice was recently reported [44]. More importantly, IgG

• tumor cells [32]. In this context and as part of ongoing research devoted to the development of selectively fluorinated MUC1 glycopeptide-based vaccines, we report herein on the successful preparation of two novel MUC1 glycoconjugates comprising 4’-deoxy-4’-fluoro-TF antigen side chains in their B cell

Synthesis of aromatic glycoconjugates. Building blocks for the construction of combinatorial glycopeptide libraries

• Markus Nörrlinger and
• Thomas Ziegler

Beilstein J. Org. Chem. 2014, 10, 2453–2460, doi:10.3762/bjoc.10.256

• linked to the backbone by a malonyl moiety were prepared via peptide coupling. The orthogonally protected glycoconjugates, bearing an acetyl-protected glycoside, were converted into their corresponding acids which are suitable building blocks for combinatorial glycopeptide synthesis. Keywords: amino

• interactions. Recently our group has prepared a series of trifunctional glycopeptide building blocks with aliphatic backbones, which allow for the automated construction of combinatorial libraries of highly divers glycopeptides suitable for studying carbohydrate–protein interactions [5][6][7][8]. Hitherto, our

• were used for combinatorial solid phase or automated spot synthesis of libraries of highly glycosylated peptides and shown to specifically bind to lectins [5][8][10]. Here, we now describe the preparation of a series of glycopeptide building blocks which allow for the construction of glycopeptide