Recyclable hypervalent-iodine-mediated solid-phase peptide synthesis and cyclic peptide synthesis

• Dan Liu,
• Ya-Li Guo,
• Jin Qu and
• Chi Zhang

Beilstein J. Org. Chem. 2018, 14, 1112–1119, doi:10.3762/bjoc.14.97

• ]. Compared with classical solution-phase peptide synthesis, the fast development of SPPS is mainly due to its short reaction time, high efficiency, low racemization, simple work-up and automation. In recent decades, various strategies, for example, native chemical ligation (NCL) [32] and serine/threonine

• ligation (STL) [33], have been reported to solve the problems occurred during the development of SPPS. Peptide synthesis in solution mediated by FPID/(4-MeOC6H4)3P is rapid (within 30 min) and efficient, at the same time the reactions proceed without racemization. Thus, it is possible and significant to

On the design principles of peptide–drug conjugates for targeted drug delivery to the malignant tumor site

• Eirinaios I. Vrettos,
• Gábor Mező and
• Andreas G. Tzakos

Beilstein J. Org. Chem. 2018, 14, 930–954, doi:10.3762/bjoc.14.80

• stabilized complex prevents the re-ligation step of DNA, catalyzed by topo I, resulting in DNA damage and therefore cell death (apoptosis). CPT is predominantly cytotoxic during the S phase replication of DNA because of the collision of the replication fork with the cleavable complex, converting the single

Phosphodiester models for cleavage of nucleic acids

• Satu Mikkola,
• Tuomas Lönnberg and
• Harri Lönnberg

Beilstein J. Org. Chem. 2018, 14, 803–837, doi:10.3762/bjoc.14.68

Synthesis and in vitro biochemical evaluation of oxime bond-linked daunorubicin–GnRH-III conjugates developed for targeted drug delivery

• Sabine Schuster,
• Beáta Biri-Kovács,
• Bálint Szeder,
• Viktor Farkas,
• László Buday,
• Zsuzsanna Szabó,
• Gábor Halmos and
• Gábor Mező

Beilstein J. Org. Chem. 2018, 14, 756–771, doi:10.3762/bjoc.14.64

• formaldehyde (e.g., from the softeners of the plastic tubes) not only during the reaction steps (cleavage, ligation) but also under the HPLC purification conditions which has a high impact on the yield [35]. Secondary structure determination by electronic circular dichroism spectroscopy ECD spectra of GnRH-III

• ) followed by ligation of Dau (oxime bond) in solution. All peptides were synthesized manually by usage of the following Fmoc-protected amino acid derivatives: Fmoc-Gly-OH, Fmoc-Pro-OH, Fmoc-Lys(Mtt)-OH, Fmoc-Lys(Dde)-OH, Fmoc-Trp-OH, Fmoc-D-Trp-OH, Fmoc-Asp(Ot-Bu)-OH, Fmoc-D-Asp(Ot-Bu)-OH, Fmoc-D-Glu(Ot-Bu

Enzyme-free genetic copying of DNA and RNA sequences

• Marilyne Sosson and
• Clemens Richert

Beilstein J. Org. Chem. 2018, 14, 603–617, doi:10.3762/bjoc.14.47

• strands catalyze splicing or ligation of longer oligonucleotides [3][4]. Ancient ribozymes might have acted as polymerases [5], inducing either the oligomerization of activated ribonucleotides or the replication of the first RNA genomes. But ribozymes are usually too long to be likely to emerge from

• more than 50 years [7]. Classical studies were often focused on ligation reactions, including templated ligations of self-complementary sequences [8][9]. Special systems, such as ligation with triplex-forming sequences [10] have produced some impressive results, and the field of ligation-based

• replication has been reviewed [11]. Ligation reactions will not be discussed further here, as they are limited in their scope, in terms of sequences, whereas monomer-based copying may be used for any given sequence, at least in principle. Rather, we will focus on copying with mononucleotides, for which early

Carbohydrate inhibitors of cholera toxin

• Vajinder Kumar and
• W. Bruce Turnbull

Beilstein J. Org. Chem. 2018, 14, 484–498, doi:10.3762/bjoc.14.34

• a non-binding mutant of the target CTB protein [66], oxidised the N-terminal threonine residue of each subunit to an aldehyde and then chemically attached GM1os ligands by oxime ligation (Figure 15). This neoglycoprotein was able to display the five copies of the carbohydrate ligand with appropriate

Stimuli-responsive oligonucleotides in prodrug-based approaches for gene silencing

• Françoise Debart,
• Christelle Dupouy and
• Jean-Jacques Vasseur

Beilstein J. Org. Chem. 2018, 14, 436–469, doi:10.3762/bjoc.14.32

• molecules with enzymatic activity. These catalytic RNAs and DNAs trigger the cleavage of RNA substrates at a specific position. Additionally, ribozymes can catalyze the ligation of target mRNA, extending their therapeutic potential to RNA repair applications. Finally, another promising ON-based therapy

Fluorogenic PNA probes

• Tirayut Vilaivan

Beilstein J. Org. Chem. 2018, 14, 253–281, doi:10.3762/bjoc.14.17

• (Figure 13) [90]. Signal amplification is also possible in the former case provided that the reaction was designed to give a ligated product that does not bind too tightly to the template, for example by using isocysteine-mediated native chemical ligation to provide a ligated PNA with a sub-optimal

• extended backbone at the ligation site [91]. Examples of the fluorogenic templated ligation of PNA are given in Table 1 which include the simple native chemical ligation of two fluorophore-labeled probes [92], formation of cyanine dyes [93][94], fluorogenic Michael addition [95][96] and cross-linking of

• dicysteine PNA probes that can bind with pro-fluorescent bisarsenical dyes [97]. Interestingly, in the native ligation reaction, the FRET efficiency increased substantially following the ligation even though the positions of the two PNA probes hardly changed [92]. It should also be noted that the selectivity

Synthetic mRNA capping

• Fabian Muttach,
• Nils Muthmann and
• Andrea Rentmeister

Beilstein J. Org. Chem. 2017, 13, 2819–2832, doi:10.3762/bjoc.13.274

• is still biologically active remains to be demonstrated [113]. Furthermore, these capping approaches can be used to produce biologically relevant RNA. U1snRNA was prepared via enzymatic ligation of a short RNA (10 nt long) containing a trimethylated m32,2,7G cap moiety to a 154 nt long RNA produced

Hydrolysis, polarity, and conformational impact of C-terminal partially fluorinated ethyl esters in peptide models

• Vladimir Kubyshkin and
• Nediljko Budisa

Beilstein J. Org. Chem. 2017, 13, 2442–2457, doi:10.3762/bjoc.13.241

• experiments are remarkably sensitive [4]. Fluorine-containing groups can be incorporated into biopolymers by various approaches, including those that utilize biosynthesis [5][6][7], enzymatic conversion [8], chemical synthesis [9][10], and ligation reactions [11]. Depending on the research target, 19F NMR

Synthesis and metal binding properties of N-alkylcarboxyspiropyrans

• Alexis Perry and
• Christina J. Kousseff

Beilstein J. Org. Chem. 2017, 13, 1542–1550, doi:10.3762/bjoc.13.154

• or under UV irradiation. Greater stabilisation of merocyanine–metal cation complexes is often achieved through the addition of extra ligation sites and this effect is particularly pronounced in structures bearing an 8′-OMe substituent with respect to binding divalent metal cations [18] (Scheme 1

Strategies toward protecting group-free glycosylation through selective activation of the anomeric center

• A. Michael Downey and
• Michal Hocek

Beilstein J. Org. Chem. 2017, 13, 1239–1279, doi:10.3762/bjoc.13.123

• ligation of an oxazoline donor and commercially available RNase B protein (with the glycans curtailed to a single GlcNAc moiety [17]) as the acceptor [16]. The beauty of this work extends beyond the enzymatic glycosylation reaction. We point out that the oxazoline functionality was installed chemically in

• thiol in moderate to excellent yield. They proposed that the oxazoline intermediate blocks access to the α-face of the molecule, hence accounting for the excellent stereoselectivity of the reaction. They then demonstrated the power of this method as a ligation strategy. The protected thiol can be

• Thermoanaerobacter thermohydrosulfuricus, which contained an unnatural N-pentenoyllysine residue at position 221. They incorporated this N-pentenoyllysine amino acid into the protein using stop-codon suppression [81][82]. The subsequent thio–ene ligation resulted in quantitative cross-linking to the protein (as

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

• two RNA enzymes can catalyze each other’s synthesis from a mixture of four different building blocks via template-directed reciprocal replication [45]. The RNA ligase molecule E can bind two oligonucleotide building blocks A’ and B’ and promote their ligation to form the ligase E’. The newly formed

• was found from in vitro evolution experiments that the introduction of G∙U base pairs close to the site of ligation leads to enhanced cross-catalytic activity. Figure 8b shows the sequence and secondary structure of the A∙B∙E’ complex. The site of ligation is indicated by the curved arrow and the G∙U

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

• the synthesis. The cyclization of the linear precursor is usually achieved by utilizing various ring-closing reactions such as Diels–Alder reactions, [15] aldol reactions, [16] copper-catalyzed azide–alkyne cycloaddition, [17][18] macrolactonization, macrolactamizations, Staudinger ligation or

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

• pharmaceutically relevant proteins contain disulfide bonds, furthermore, the disulfide ligation and its established chemoselectivity is of great advantage for proteins’ functionalization [5]. In addition, disulfides also play valuable roles as versatile building blocks for industrial applications [6][7][8]. Thus

Energy down converting organic fluorophore functionalized mesoporous silica hybrids for monolith-coated light emitting diodes

• Markus Börgardts and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2017, 13, 768–778, doi:10.3762/bjoc.13.76

• , stable structures like silica-based materials, in particular mesoporous silica, offer favorable properties [4][10]. Eventually, organic–inorganic hybrid materials can be easily accessed by covalent ligation of the functional guest chromophore to a silica host matrix [11][12]. As a consequence the

Correction: 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. 2017, 13, 301–302, doi:10.3762/bjoc.13.32

• : building blocks; coalescence; dynamic NMR; labeling; Staudinger ligation; In the original article an incorrect caption for Figure 1 was given. The assignment of the solvents to the capital letters was not correct. The correct caption of Figure 1 is: 1H NMR spectra of compound 3a measured in five different

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

• applicability of these compounds as possible 18F-building blocks, two biomolecules were modified and chosen for conjugation either using the Huisgen-click reaction or the traceless Staudinger ligation. Keywords: building blocks; coalescence; dynamic NMR; labeling; Staudinger ligation; Introduction The

• connection to the label (e.g., fluorescence dye, radionuclide) and the second is used for the introduction of a (bioorthogonal) functional group (e.g., azide, alkyne, phosphane, tetrazine) to later connect to the biomolecule via bioorthogonal ligation. Our aim was the development of novel, N,N

• to demonstrate the Cu-catalyzed azide–alkyne click reaction (Huisgen 1,3-dipolar cycloaddition) and the traceless Staudinger ligation, a proof of concept study was performed for the site-selective labeling of a pharmacologically active peptide and a small organic compound. These compounds provide the

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

• characteristics, outstanding stability, regular fibrous architecture and high synthetic accessibility with numerous chemoselective ligation and modification methods [24][25][26]. Also, various post-translational modifications, like phosphorylation or glycosylation have been studied as aggregation triggers [27][28

A new paradigm for designing ring construction strategies for green organic synthesis: implications for the discovery of multicomponent reactions to build molecules containing a single ring

• John Andraos

Beilstein J. Org. Chem. 2016, 12, 2420–2442, doi:10.3762/bjoc.12.236

• order to complete the ligation to the five-membered pyrazole ring. A literature search revealed that there were no documented examples of the A2, A3, B1, B2, B3, and B5 strategies, which indicates that the chemical space for three-component coupling reactions to pyrazole has not yet been fully explored

Enduracididine, a rare amino acid component of peptide antibiotics: Natural products and synthesis

• Darcy J. Atkinson,
• Briar J. Naysmith,
• Daniel P. Furkert and
• Margaret A. Brimble

Beilstein J. Org. Chem. 2016, 12, 2325–2342, doi:10.3762/bjoc.12.226

• ). Saponification of the ester of 88 and coupling with H-Ser(Bn)-O-Allyl and treatment with HCl afforded dipeptide 89. A second peptide coupling with acid 90 then gave tripeptide 78. With tripeptide 78 in hand, ligation with the remaining tripeptide 71 followed by cyclisation and global deprotection afforded the

p-Nitrophenyl carbonate promoted ring-opening reactions of DBU and DBN affording lactam carbamates

• Madhuri Vangala and
• Ganesh P Shinde

Beilstein J. Org. Chem. 2016, 12, 2086–2092, doi:10.3762/bjoc.12.197

• carbohydrate–protein interactions [25], ligation and surfactant properties [26][27]. Although p-nitrophenyl carbonates were extensively utilized in these reactions, the nucleophilicity of amidine bases towards these carbonates was not encountered so far. In continuation of our interest in carbohydrates [28][29

Thiophene-forming one-pot synthesis of three thienyl-bridged oligophenothiazines and their electronic properties

• Dominik Urselmann,
• Konstantin Deilhof,
• Bernhard Mayer and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2016, 12, 2055–2064, doi:10.3762/bjoc.12.194

• and for all three structures this longest wavelength absorption can be assigned to S1 states that predominantly consist of HOMO to LUMO transitions with dominant oscillator strengths. For the thienyl-bridged 2,5-bis(terphenothiazinyl)thiophene 3c, containing the symmetrical conjugative ligation of two

Economical and scalable synthesis of 6-amino-2-cyanobenzothiazole

• Jacob R. Hauser,
• Hester A. Beard,
• Mary E. Bayana,
• Katherine E. Jolley,
• Stuart L. Warriner and
• Robin S. Bon

Beilstein J. Org. Chem. 2016, 12, 2019–2025, doi:10.3762/bjoc.12.189

• luciferin scaffolds [2][5][8]. Even in the presence of other thiols and amines, CBTs react rapidly and selectively with 1,2-aminothiols under physiological conditions. This selective and bioorthogonal reactivity of CBTs has been exploited in the development of the CBT ligation as a useful and fast

• bioorthogonal ligation and bioluminescent imaging. The procedure allowed the safe synthesis of 8 at multigram scale and in high purity. In addition, the sole use of filtrations and crystallisations for purification of all intermediates and products, in combination with the endothermic nature of the controlled

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

• yet been demonstrated experimentally. (b) Peptidase-like macrolactam formation An alternative route to macrolactams involves the use of protease-like proteins that catalyse cyclisation via a ping-pong mechanism [85][104][105] (Figure 8A). In fact, protease-mediated ligation is a well-established

• macrocylisation of other cyclic plant RiPPs, including kalata-type cyclotides [85] (Figure 8C) and cyclic knottins [116], especially because the ligation site almost always features an Asx residue. Clitoria ternatea is a tropical plant that produces cylotides, and a remarkably efficient peptide ligase, butelase 1

• capacity to catalyse cyclisation [116]. Butelase 1 can also catalyse peptide ligation when a short C-terminal sequence motif of NHV is used as the acceptor, where N is the site of ligation. Conversely, the well-characterised peptide ligase sortase A (SrtA) has been employed to catalyse cyclisation using a