A self-assembled cyclodextrin nanocarrier for photoreactive squaraine

• Ulrike Kauscher and
• Bart Jan Ravoo

Beilstein J. Org. Chem. 2016, 12, 2535–2542, doi:10.3762/bjoc.12.248

• complexation. In that way, it was possible to decorate CDVs with carbohydrates [32][33], with peptides [34], and also with DNA [35]. Moreover CDVs were also shown to form very dense membranes in combination with phospholipids and cholesterol [36]. Previous studies also showed promising results for PDT

Synthesis, dynamic NMR characterization and XRD studies of novel N,N’-substituted piperazines for bioorthogonal labeling

• Constantin Mamat,
• Marc Pretze,
• Matthew Gott and
• Martin Köckerling

Beilstein J. Org. Chem. 2016, 12, 2478–2489, doi:10.3762/bjoc.12.242

• bioorthogonal 18F-containing building blocks The development of new 18F-based radiotracers remains an ongoing goal in the field of radiopharmacy and provides tools for specific cancer diagnostics using positron emission tomography (PET) [31][32][33]. When radiotracers are based on tumor-specific peptides

Inhibition of peptide aggregation by means of enzymatic phosphorylation

• Kristin Folmert,
• Malgorzata Broncel,
• Hans v. Berlepsch,
• Christopher H. Ullrich,
• Mary-Ann Siegert and
• Beate Koksch

Beilstein J. Org. Chem. 2016, 12, 2462–2470, doi:10.3762/bjoc.12.240

• ; peptide phosphorylation; protein folding; Introduction Amyloid fibrils are one of the most important and studied self-assembled materials in nature. A wide range of peptides and proteins with various primary sequences and functions are able to form these wel organized and highly stable aggregates under

• the subject of numerous studies, the pathway of aggregation from soluble α-helical-rich or partially unfolded peptides into insoluble β-sheet-rich amyloid fibrils remains unclear. Several studies discovered parameters of peptide environment, like pH [12][13], oxidative stress [14], presence of organic

• components [15][16] or metal ions [17][18], to have a crucial influence on the conformational transition. The challenging physicochemical properties, the low solubility and the tendency to aggregate make natural amyloid-forming peptides difficult to synthesize and complicates detailed structural

β-Amino functionalization of cinnamic Weinreb amides in ionic liquid

• Yi-Ning Wang,
• Guo-Xiang Sun and
• Gang Qi

Beilstein J. Org. Chem. 2016, 12, 2372–2377, doi:10.3762/bjoc.12.231

• , but also in important building blocks widely used in the organic syntheses. They are especially used in the synthesis of β-amino acids [4][5], which are precursors for many biological and pharmacological active compounds, such as β-lactams [6] and β-peptides [7]. The most straightforward approach

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

• separation of the two anomeric amide protons of the rotamers of 1a were observed and no cleavage of the Fmoc group occurred. Höck et al. [24] could also show that chlorobenze-d5 does not cause cleavage of Fmoc groups in peptides up to 120 °C. Figure 9 shows the temperature-dependent 1H NMR spectra (7.65–8.30

From supramolecular chemistry to the nucleosome: studies in biomolecular recognition

• Marcey L. Waters

Beilstein J. Org. Chem. 2016, 12, 1863–1869, doi:10.3762/bjoc.12.175

• -helices; aromatic interactions; β-hairpin peptides; cation–π interactions; dynamic combinatorial chemistry; histone; molecular recognition in water; nucleosome; π–π-stacking; post-translational modification; supramolecular chemistry; Review Childhood influences When thinking about how to start writing

• model systems to study these interactions in aqueous solution and to gain insight into the nature of these interactions, their biological relevance, and also see if we could use them to influence structure and function. Peptides were very appealing because of the ease of synthesis and the ease of

• ][26][27][28][29][30][31][32]. At the same time, our model systems provided significant insight into the features that contribute to folding of β-hairpin peptides and β-sheets, an area that lagged decades behind the general understanding of α-helices. Beyond using β-hairpins as scaffolds for physical

Three-component synthesis of highly functionalized aziridines containing a peptide side chain and their one-step transformation into β-functionalized α-ketoamides

• Lena Huck,
• Juan F. González,
• Elena de la Cuesta and
• J. Carlos Menéndez

Beilstein J. Org. Chem. 2016, 12, 1772–1777, doi:10.3762/bjoc.12.166

• for the preparation of peptides [2][3] and the synthesis of peptide-like compounds comprising the aziridine motif [4][5]. Furthermore, the incorporation of an electrophilic aziridine moiety in peptide or peptidomimetic frameworks is an interesting strategy for the design of active site-directed drugs

Organic chemistry meets polymers, nanoscience, therapeutics and diagnostics

• Vincent M. Rotello

Beilstein J. Org. Chem. 2016, 12, 1638–1646, doi:10.3762/bjoc.12.161

• demonstrated this templation with peptides [23] and are (still!) trying to definitively show templation to proteins. As I mentioned above, I am an incessant tinkerer, a trait that has rubbed off on the group. When students mixed complementary versions of the polymers and nanoparticles described above, we were

Biosynthesis of oxygen and nitrogen-containing heterocycles in polyketides

• Franziska Hemmerling and
• Frank Hahn

Beilstein J. Org. Chem. 2016, 12, 1512–1550, doi:10.3762/bjoc.12.148

• [4]. Oxygen heterocycles are mainly found in carbohydrates, polyketides, peptides and terpenoids. Nitrogen heterocycles are part of peptides and alkaloids. Both can of course also occur in the respective hybrid natural products. Sulphur-containing heterocycles are present in few polyketides and more

Application of Cu(I)-catalyzed azide–alkyne cycloaddition for the design and synthesis of sequence specific probes targeting double-stranded DNA

• Svetlana V. Vasilyeva,
• Vyacheslav V. Filichev and
• Alexandre S. Boutorine

Beilstein J. Org. Chem. 2016, 12, 1348–1360, doi:10.3762/bjoc.12.128

• ]. Besides natural and engineered peptides or proteins, two synthetic substances are known to recognize and bind dsDNA in a sequence-specific manner: triplex-forming oligonucleotides (TFOs) [4][5] and pyrrole–imidazole polyamide minor groove binders (MGBs) [6][7]. TFOs recognize polypurine stretches in

Cyclisation mechanisms in the biosynthesis of ribosomally synthesised and post-translationally modified peptides

• Andrew W. Truman

Beilstein J. Org. Chem. 2016, 12, 1250–1268, doi:10.3762/bjoc.12.120

• Andrew W. Truman Department of Molecular Microbiology, John Innes Centre, Colney Lane, Norwich, NR4 7UH, UK 10.3762/bjoc.12.120 Abstract Ribosomally synthesised and post-translationally modified peptides (RiPPs) are a large class of natural products that are remarkably chemically diverse given an

• heterocyclisation to form thiazolines or oxazolines, and radical-mediated reactions between unactivated carbons. Future prospects for RiPP pathway discovery and characterisation will also be highlighted. Keywords: biosynthesis; cyclisation; enzymes; peptides; RiPPs; Introduction Nature employs a number of routes

• to produce peptidic secondary metabolites, including non-ribosomal peptide synthetases [1][2] (NRPSs) and diketopiperazine-forming cyclases [3][4]. Alternatively, peptides synthesised by the ribosome can be post-translationally modified into secondary metabolites [5]. These are termed ribosomally

Marine-derived myxobacteria of the suborder Nannocystineae: An underexplored source of structurally intriguing and biologically active metabolites

• Antonio Dávila-Céspedes,
• Peter Hufendiek,
• Max Crüsemann,
• Till F. Schäberle and
• Gabriele M. König

Beilstein J. Org. Chem. 2016, 12, 969–984, doi:10.3762/bjoc.12.96

• metabolites can be found in various detailed reports [19][20][21][22][23]. The majority of these metabolites are either non-ribosomal peptides, e.g., cystobactamids 1–3 (Figure 1) [24], polyketides, e.g., aurafuron A (4) [25], or hybrids thereof, e.g., corallopyronin A (5, Figure 2) [26]. Interestingly, an

• gene clusters, among them three NRPS, two PKS, three NRPS/PKS and four ribosomal peptides (see Table 1). Apart from homologies to geosmin (100%), aurafuron (71%) and paneibactin (50%) biosynthetic genes, the gene clusters display a large degree of novelty. Recently, the biosynthetic gene cluster of

Muraymycin nucleoside-peptide antibiotics: uridine-derived natural products as lead structures for the development of novel antibacterial agents

• Daniel Wiegmann,
• Stefan Koppermann,
• Marius Wirth,
• Giuliana Niro,
• Kristin Leyerer and
• Christian Ducho

Beilstein J. Org. Chem. 2016, 12, 769–795, doi:10.3762/bjoc.12.77

• ; natural products; nucleosides; peptides; structure–activity relationship; Introduction The treatment of infectious diseases caused by bacteria is a severe issue. With multiresistant bacterial strains rendering well-established therapeutic procedures ineffective, the exploration of novel antimicrobial

Gold-catalyzed direct alkynylation of tryptophan in peptides using TIPS-EBX

• Gergely L. Tolnai,
• Jonathan P. Brand and
• Jerome Waser

Beilstein J. Org. Chem. 2016, 12, 745–749, doi:10.3762/bjoc.12.74

• Givaudan, Chemin de la parfumerie 5, 1214 Vernier, Switzerland 10.3762/bjoc.12.74 Abstract The selective functionalization of peptides containing only natural amino acids is important for the modification of biomolecules. In particular, the installation of an alkyne as a useful handle for bioconjugation

• is highly attractive, but the use of a carbon linker is usually required. Herein, we report the gold-catalyzed direct alkynylation of tryptophan in peptides using the hypervalent iodine reagent TIPS-EBX (1-[(triisopropylsilyl)ethynyl]-1,2-benziodoxol-3(1H)-one). The reaction proceeded in 50–78% yield

• under mild conditions and could be applied to peptides containing other nucleophilic and aromatic amino acids, such as serine, phenylalanine or tyrosine. Keywords: alkynes; C–H functionalization; gold catalysis; hypervalent iodine; peptides; Introduction Alkynes have always been important building

From steroids to aqueous supramolecular chemistry: an autobiographical career review

• Bruce C. Gibb

Beilstein J. Org. Chem. 2016, 12, 684–701, doi:10.3762/bjoc.12.69

• -helical peptides could be coupled to the rim of a cavitand scaffold to form mimics of four-helix bundles or caviteins (Figure 2) [9][10]. These latter two projects worked well, although I ended up moving on before the cavitein work could be brought to full fruition; it was more a case of me ”clearing the

Antibiotics from predatory bacteria

• Juliane Korp,
• María S. Vela Gurovic and
• Markus Nett

Beilstein J. Org. Chem. 2016, 12, 594–607, doi:10.3762/bjoc.12.58

• via horizontal gene transfer. Cystobactamids: The cystobactamids were recently isolated from a Cystobacter sp. and represent a novel class of NRPS-derived antimicrobial peptides [113]. Cystobactamids 919-1 and 919-2 (Figure 5) display an unusual aromatic scaffold composed of p-nitrobenzoic acid and

Studies on the synthesis of peptides containing dehydrovaline and dehydroisoleucine based on copper-mediated enamide formation

• Franziska Gille and
• Andreas Kirschning

Beilstein J. Org. Chem. 2016, 12, 564–570, doi:10.3762/bjoc.12.55

• protecting group and the reaction conditions. It was found that ornithine – a suitable precursor – is better suited than arginine for achieving good yields for the C–N cross-coupling reaction. The optimized conditions were utilized for the synthesis of peptides 32, 33, 39 and 40 containing a neighboring

• ornithine as well as for the tripeptide 44 containing dehydroisoleucine with the correct stereochemistry. Keywords: catalysis; dehydroamino acids; Hartwig–Buchwald reaction; myxovalargin; peptides; Introduction Dehydroamino acids [1] are rare amino acids that are constituents of many oligopeptides from

• microbial sources. Typical examples are myxovalargin (1), argyrin (2) and nisin (3, Scheme 1). Dehydroamino acids and peptides are characterized by the presence of an olefinic double bond conjugated with the carboxyl or peptidic carbonyl group. Besides being α,β-unsaturated acids or amides, respectively

Art, auto-mechanics, and supramolecular chemistry. A merging of hobbies and career

• Eric V. Anslyn

Beilstein J. Org. Chem. 2016, 12, 362–376, doi:10.3762/bjoc.12.40

• electronic tongue and chemometrics were methods to differentiate ATP, GTP and AMP [92], phosphorylated peptides [93], as well as a technique to identify sweeteners in coffee and tea [94]. Each of these studies used combinatorial libraries of peptides around a preorganized scaffold or with a known targeting

• our group are on wines. As with our earlier work, the approach uses a suite of combinatorial peptides as differential receptors. The peptides are biased with a large fraction of the amino acid histidine, are metallated with Cu, Ni, and Zn, and bind indicators to create a series of IDAs that can

• peptides that respond to only one kinase [108][109]. This can be viewed as a lock and key approach, while as described herein, many groups have shown that the differential sensing approach may be more applicable for certain applications. Thus, we took a suite of peptides containing the SOX fluorophore, and

Enabling technologies and green processes in cyclodextrin chemistry

• Giancarlo Cravotto,
• Marina Caporaso,
• Laszlo Jicsinszky and
• Katia Martina

Beilstein J. Org. Chem. 2016, 12, 278–294, doi:10.3762/bjoc.12.30

• and a high electrochemical response [74]. CuAAC has been successfully used to immobilize molecules on polymers and biopolymers as well as to join sugars to peptides and proteins. CD-polyglycerol dendron amphiphiles (CD-PG) have also been obtained. This derivative showed high encapsulation efficiency

My maize and blue brick road to physical organic chemistry in materials

• Anne J. McNeil

Beilstein J. Org. Chem. 2016, 12, 229–238, doi:10.3762/bjoc.12.24

• system, similar trends were observed. To determine whether these results were general, postdoctoral researcher Maria Muro-Small synthesized and measured dissolution enthalpies for 11 dipeptide-based compounds (6 gelators, 5 nongelators) [33]. Peptides were chosen because they represent the largest and

A journey in bioinspired supramolecular chemistry: from molecular tweezers to small molecules that target myotonic dystrophy

• Steven C. Zimmerman

Beilstein J. Org. Chem. 2016, 12, 125–138, doi:10.3762/bjoc.12.14

• context of analyzing the vancomycin complex with D–Ala–D–Ala containing peptides, suggested the cost of freezing a free rotation to be between 0.4 to 0.9 kcal/mol – a value that is also close to what we had measured [25]. In Williams’ case, the value was derived from the entropy of fusion within a

• , materials and medicine.” Some of the examples presented herein illustrate the potential of the supramolecular approach to lead to advanced therapeutic agents. In particular the Klärner molecular tweezers that complex lysine-containing peptides may lead to agents that dissolve Alzheimers plaques or inhibit

Selectively fluorinated cyclohexane building blocks: Derivatives of carbonylated all-cis-3-phenyl-1,2,4,5-tetrafluorocyclohexane

• Mohammed Salah Ayoup,
• David B. Cordes,
• Alexandra M. Z. Slawin and
• David O'Hagan

Beilstein J. Org. Chem. 2015, 11, 2671–2676, doi:10.3762/bjoc.11.287

• demonstrated that 4 can be elaborated in a relatively straightforward manner by mainstream reactions of electrophilic aromatic substitution [7]. This extended to the synthesis of cyclohexane substituted (S)-L-phenylalanines with orthogonal protecting groups suitable for their incorporation into peptides [8

Assembly of synthetic Aβ miniamyloids on polyol templates

• Sebastian Nils Fischer and
• Armin Geyer

Beilstein J. Org. Chem. 2015, 11, 2646–2653, doi:10.3762/bjoc.11.284

• Sebastian Nils Fischer Armin Geyer Faculty of Chemistry, Philipps University Marburg, Hans-Meerwein-Straße 4, 35032 Marburg, Germany 10.3762/bjoc.11.284 Abstract Covalent dynamic chemistry is used to mimic the first steps of the highly cooperative fibril formation of Aβ peptides. For that purpose

• boronic esters with peptides of type 1 and 2. Nuclear magnetic resonance can differentiate between regioisomeric boronic esters and identifies preferred sites of esterification on the dimeric template 9. 2-Formylphenylboronic acid (14) is used to link the parent pentapeptide Leu-Val-Phe-Phe-Ala to the

• template 16 to obtain threefold boronic ester 17. The miniamyloid 17 assembles from seven components by imine and boronic ester bonds between the peptides and the template. The relative orientation and spacing of the peptides mimic the assembly of peptides in Alzheimer β-amyloids. Keywords: Alzheimer

Recent highlights in biosynthesis research using stable isotopes

• Jan Rinkel and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2015, 11, 2493–2508, doi:10.3762/bjoc.11.271

• classes including polyketides, non-ribosomal peptides, their hybrids, terpenoids, and aromatic compounds formed via the shikimate pathway. The text does not aim at a comprehensive overview, but instead a selection of recent important examples of isotope usage within biosynthetic studies is presented, with

• ], but these aspects will not be discussed here. Instead, this review highlights recent biosynthetic studies using isotopes from major classes of natural products including polyketides, non-ribosomal peptides, hybrids thereof, isoprenoids and a few aromatic compounds that arise via the shikimate pathway

• -ribosomal peptides Non-ribosomal peptides often exhibit a high bioactivity and are biosynthesized by non-ribosomal peptide synthethases (NRPS) [33], which work RNA-independent and catalyze the assembly of both proteinogenic and non-proteinogenic amino acids in a modular fashion. Moreover, NRPSs can contain

Diversity-oriented synthesis of analogues of the novel macrocyclic peptide FR-225497 through late stage functionalization

• Jyotiprasad Mukherjee,
• Suman Sil and
• Shital Kumar Chattopadhyay

Beilstein J. Org. Chem. 2015, 11, 2487–2492, doi:10.3762/bjoc.11.270

• -225497. Keywords: cross metathesis; cyclic peptides; diversity oriented synthesis; macrocycle; Introduction Diversity-oriented synthesis (DOS) has been established as an important paradigm in drug discovery [1][2][3][4][5][6][7]. Although the major focus is on the synthesis of small molecular libraries

• peptides of the general structure 1 (Figure 1) displays important histone deacetylase inhibition property relevant to drug design against a number of diseases ranging from antifungal, antimicrobial to arrest of proliferation of several cell types of epithelial and hematological origin [13]. The compounds