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

• coupling reagent, which was developed by Ye’s group in order to reduce racemization and side reactions [50]. The precursor 2 was obtained via successive deprotection of the C-terminal and the N-terminal protecting group of 14. The overall yield of this route is 28%. With the precursor 2 in hand, we then

An overview of recent advances in duplex DNA recognition by small molecules

• Sayantan Bhaduri,
• Nihar Ranjan and
• Dev P. Arya

Beilstein J. Org. Chem. 2018, 14, 1051–1086, doi:10.3762/bjoc.14.93

• hydrophobic interactions (Figure 2). Figure 2a shows that the arginine side chain of the MATα2 N-terminal arm facilitates interaction between portions of the heterodimer MATα1–MATα2 with the minor groove of the DNA substrate by forming alternate H-bond interactions [25]. The main characteristic feature of

• lipophilicity [53]. These structural analogs comprise of branched N-alkyl- and N-cycloalkylpyrroles to test the conformational flexibility towards DNA binding. Hydrophobic N-terminal amides and substituted thiazole replacing pyrrole were installed in order to impart more lipophilicity. All these compounds were

• shown to bind A·T-rich regions preferentially. The compounds containing branched N-alkylpyrrole, hydrophobic N-terminal amide, and especially C-isopropylthiazole (thiazotropsin A as shown in the Figure 4) showed significant antimicrobial activity against MRSA and Candida albicans strains. Thiazotropsin

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

• on its building block 2-pyrrolino-DOX and tried to construct new PDCs using other peptides. Therefore, they synthesized a new analog, designated AN-238, consisting of the octapeptide RC-121 linked through the α-amino group of its N-terminal D-Phe moiety and a glutaric acid spacer to the 14-OH group

Development of novel cyclic NGR peptide–daunomycin conjugates with dual targeting property

• Andrea Angelo Pierluigi Tripodi,
• Szilárd Tóth,
• Kata Nóra Enyedi,
• Gitta Schlosser,
• Gergely Szakács and
• Gábor Mező

Beilstein J. Org. Chem. 2018, 14, 911–918, doi:10.3762/bjoc.14.78

• homing devices may provide dual targeted delivery of anticancer drugs. According to literature data, one of the most stable and tumor-selective cyclic NGR-peptides is c[KNGRE]-NH2, in which the α-amino group of the N-terminal Lys is coupled to the γ-carboxyl group of the glutamic acid residue (head-to

Volatiles from three genome sequenced fungi from the genus Aspergillus

• Jeroen S. Dickschat,
• Ersin Celik and
• Nelson L. Brock

Beilstein J. Org. Chem. 2018, 14, 900–910, doi:10.3762/bjoc.14.77

• ). A phylogenetic analysis of 878 fungal terpene synthase homologs (Figure S1 in Supporting Information File 1) demonstrates that this enzyme is closely related to the bifunctional ent-copalyl diphosphate synthase/ent-kaurene synthase from Fusarium fujikuroi [33]. The N-terminal domain shows the DXDD

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

• nucleic acids (PNAs), a lipophilic triphenylphosphonium (TPP) cation was attached to the N-terminal extremity of a PNA through a biodegradable carbamate linker containing a disulfide bridge (Scheme 4B) [20]. It was shown that such PNA conjugates entered cells rapidly and efficiently. Furthermore, a 16-mer

Position-dependent impact of hexafluoroleucine and trifluoroisoleucine on protease digestion

• Susanne Huhmann,
• Anne-Katrin Stegemann,
• Kristin Folmert,
• Damian Klemczak,
• Johann Moschner,
• Michelle Kube and
• Beate Koksch

Beilstein J. Org. Chem. 2017, 13, 2869–2882, doi:10.3762/bjoc.13.279

• this study when positioned N-terminal to the cleavage site. These results provide valuable information for the application of fluorinated amino acids in the design of proteolytically stable peptide-based pharmaceuticals. Keywords: fluorinated amino acids; hexafluoroleucine; peptide drugs; protease

• enzymes in humans. It exhibits specificity for hydrophobic, especially aromatic residues like Phe, Trp, and Tyr at the P1 and P1’ positions [50][51][52][53][54]. It has an extended active site that can bind at least seven residues [66][67], and peptide bond cleavage occurs N-terminal to the residue at

• ). Only P2’-HfLeuFA is not hydrolyzed at the designed cleavage site, instead cleavage occurs exclusively N-terminal to the HfLeu residue, thus demonstrating that HfLeu occupies the P1’ position. In the case of P2’-TfIle we found two further peptide bonds that are cleaved by pepsin, namely N-terminal

Synthetic mRNA capping

• Fabian Muttach,
• Nils Muthmann and
• Andrea Rentmeister

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

• ]. Peyrane et al. demonstrated that using the N-terminal fragment bearing the primase activity resulted in comparable preparation yield for the RNA while expression and solubility of the fragment were improved [53]. mRNA cap analogues Preparation of cap analogues The co-transcriptional capping described

• pioneering work of the Rosenberg group [35]. To date, the capping enzymes from the Vaccinia virus are commercially available and most widely used for post-transcriptional in vitro capping. They consist of two viral proteins D1 and D12. The triphosphatase and guanylyltransferase activity are located in the N

• -terminal half and the methyltransferase in the C-terminal half of the large D1 protein, whereas the small D12 protein has no catalytic activity but activates D1 [36][37][38]. Originally, the RNA capping with the Vaccinia capping apparatus was reported to be inefficient [35][37][39][40]. To date, the enzyme

Development of a fluorogenic small substrate for dipeptidyl peptidase-4

• Futa Ogawa,
• Masanori Takeda,
• Kanae Miyanaga,
• Keita Tani,
• Ryuji Yamazawa,
• Kiyoshi Ito,
• Atsushi Tarui,
• Kazuyuki Sato and
• Masaaki Omote

Beilstein J. Org. Chem. 2017, 13, 2690–2697, doi:10.3762/bjoc.13.267

• fluorescence push–pull system would be destroyed. To confirm this, we modified 1 to provide a peptidic substrate for an enzyme. The serine protease DPP-4 was used as the test enzyme because its substrate specificity is clear: it hydrolyses the C-terminal of proline or alanine second to the N-terminal of the

Recent progress in the racemic and enantioselective synthesis of monofluoroalkene-based dipeptide isosteres

• Myriam Drouin and
• Jean-François Paquin

Beilstein J. Org. Chem. 2017, 13, 2637–2658, doi:10.3762/bjoc.13.262

• methyl ester using trimethylsilyldiazomethane, followed by its reduction to the corresponding alcohol and a Mitsunobu reaction, permitted the incorporation of the N-terminal moiety. Then, removal of the Ns group of 28 and deprotection of the primary alcohol was performed to obtain 29 which underwent a

• ). The resulting ester 33 was then reduced to the corresponding aldehyde, followed by the formation of the terminal imine and its subsequent reduction to access the N-terminal moiety of 34. The alcohol and the amine deprotections were then achieved, followed by reprotection of the amine with a

• synthesized by a HWE olefination of the chiral cyclopentanone 101 (Scheme 20) [54]. The resulting ester was converted into the aldehyde and β-fluoroenimine 104 was obtained using Ellman’s conditions. At this stage, the lateral chain of the N-terminal residue was added by an alkylation reaction using a

What contributes to an effective mannose recognition domain?

• Christoph P. Sager,
• Deniz Eriş,
• Martin Smieško,
• Rachel Hevey and
• Beat Ernst

Beilstein J. Org. Chem. 2017, 13, 2584–2595, doi:10.3762/bjoc.13.255

• enables uropathogenic Escherichia coli (UPEC) to adhere to urothelial host cells [33][34], which represents the first and most critical step in UTI, triggering a cascade of pathogenic processes ultimately leading to infection. The ligand on urothelial cells binding to the N-terminal lectin domain of FimH

Mechanochemical synthesis of small organic molecules

• Tapas Kumar Achar,
• Anima Bose and
• Prasenjit Mal

Beilstein J. Org. Chem. 2017, 13, 1907–1931, doi:10.3762/bjoc.13.186

• NaHCO3 (base); 2) esterification of N-protected amino acid using different dialkyl dicarbonate or alkyl chloroformate in the presence of DMAP as catalyst and followed by acidic workup. For N-terminal protection, different precursors like Fmoc-Cl, benzoyl chloride and Boc2O were used successfully to get

2-Methyl-2,4-pentanediol (MPD) boosts as detergent-substitute the performance of ß-barrel hybrid catalyst for phenylacetylene polymerization

• Julia Kinzel,
• Daniel F. Sauer,
• Marco Bocola,
• Marcus Arlt,
• Tayebeh Mirzaei Garakani,
• Andreas Thiel,
• Klaus Beckerle,
• Tino Polen,
• Jun Okuda and
• Ulrich Schwaneberg

Beilstein J. Org. Chem. 2017, 13, 1498–1506, doi:10.3762/bjoc.13.148

• the β-barrel membrane channel protein FhuA WT co-crystallized with the detergent n-octyl-2-hydroxyethyl sulfoxide [24]. The N-terminal cork domain (residue 1-160) blocking the channel was removed. The amino acid exchanges of the hybrid catalyst model FhuA ΔCVFtev, namely cysteine at position 545

Characterization of non-heme iron aliphatic halogenase WelO5* from Hapalosiphon welwitschii IC-52-3: Identification of a minimal protein sequence motif that confers enzymatic chlorination specificity in the biosynthesis of welwitindolelinones

• Qin Zhu and
• Xinyu Liu

Beilstein J. Org. Chem. 2017, 13, 1168–1173, doi:10.3762/bjoc.13.115

• vector pQTEV. Heterologous expression in E. coli and purification by immobilized metal affinity chromatography (IMAC) gave the N-terminal hepta-His-tagged WelO5* in a comparable yield (20 mg/L) as for WelO5 [11]. With abundant WelO5* in hand, we proceeded on its in vitro characterization using the assay

Glycoscience@Synchrotron: Synchrotron radiation applied to structural glycoscience

• Serge Pérez and
• Daniele de Sanctis

Beilstein J. Org. Chem. 2017, 13, 1145–1167, doi:10.3762/bjoc.13.114

• characterization, the lectin, BC2L-C was shown to be composed of two distinct domains, each displaying unique specificities and biological activities. The protein is a super lectin that binds independently to fucosylated human histo-blood group epitopes and to mannose/heptose glycoconjugates. The N-terminal domain

Synthesis and enzymatic ketonization of the 5-(halo)-2-hydroxymuconates and 5-(halo)-2-hydroxy-2,4-pentadienoates

• Tyler M. M. Stack,
• William H. Johnson Jr. and
• Christian P. Whitman

Beilstein J. Org. Chem. 2017, 13, 1022–1031, doi:10.3762/bjoc.13.101

• -terminal methionine, the same enzyme with an N-formylmethionine, the intact enzyme with an N-terminal methionine, and the intact enzyme with an N-formylmethionine [25]. Synthesis of ethyl 2-fluorocrotonate and ethyl 2-bromocrotonate Ethyl 2-fluorocrotonate was synthesized following published procedures [18

• mass (6916 Da). In addition to this species (corresponding to the intact enzyme without the N-formylmethionine), there are five additional signals at 6475 Da, 6606 Da, 6634 Da, 7046 Da, and 7076 Da. These signals correspond to enzyme without the four C-terminal amino acids, the same enzyme with an N

Opportunities and challenges for the sustainable production of structurally complex diterpenoids in recombinant microbial systems

• Katarina Kemper,
• Max Hirte,
• Markus Reinbold,
• Monika Fuchs and
• Thomas Brück

Beilstein J. Org. Chem. 2017, 13, 845–854, doi:10.3762/bjoc.13.85

• example of these bifunctional enzymes was published by Chen and coworkers [60], who managed to crystalize catalytic domains of PaFS, a diterpene synthase from Phomopsis amygdali. The formation of GGPP is located in a C-terminal α-domain with very low sequence identity to the N-terminal Class I terpene

• engineered for functional and soluble expression in prokaryotic hosts like E. coli, Removal of the N-terminal and thereby the cell-wall-localization domain (indicated through scissors) is a standard procedure in engineering plant enzymes; 3: Further engineering steps are not mandatory but often entail site

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

• isoprenylated by ComQ is located at either the 3rd or 4th position from the C-terminal end, and the cleavage of the N-terminal residues leads to the production of the mature ComX pheromone with six to ten amino acid residues (Figure 5). In most ribosomally synthesized and posttranslationally modified peptides

• (RIPPs), a conserved recognition motif in the N-terminal leader region of the precursor peptide enables the enzymatic modification of the C-terminal core peptide, and then the leader amino acids are frequently cleaved [2]. However, there is no obvious sequence within the N-terminal region of the ComX

• amino acid residues, the N-terminal leucine residue and the modified tryptophan residue were the only conserved amino acids in the ComX variants. Therefore, a common consensus sequence for tryptophan isoprenylation does not seem to exist. In addition, the tryptophan residue modified with a geranyl group

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

• -Hpg7 peptide as well as the mono- and bicyclic products based on P450-catalysed turnover have been analysed in earlier studies [13][16][17]. Prior to the activity assay the substrate was loaded onto the A47934 PCP-X di-domain construct exhibiting maltose binding protein as N-terminal fusion partner

• the low levels of StaH activity [12]. In order to analyse if this effect is maintained over the subsequent amino acid cyclisation reactions in A47934 biosynthesis, we tested StaF activity using the same constructs all exhibiting MBP as N-terminal fusion partner: a PCP-X construct from A47934

• conformation of the B–C loop, which exhibits a helical part in OxyAtei in contrast to StaF, and the position of the F and G helices, which are drawn down towards the centre of the protein in StaF closing the active site to a greater extent than observed for OxyAtei. In both the StaF structures, the N-terminal

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

• site specific labelling of PqsD Next, we were interested to investigate if any of the ABPP probes was capable of labelling PqsD. Therefore, we cloned the pqsD gene of Pseudomonas aeruginosa PAO1 into an expression vector encoding an N-terminal strep-tag. The protein was heterologously expressed in

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

• spectra were averaged over three scans (λ = 195–240 nm; 0.5 nm intervals; 2 mm bandwidth; 4 s response time, 100 nm min−1 scanning speed). Ellipticity was normalized to concentration (c [mol L−1]), number of residues (n = 27, including the N-terminal Abz group) and path length (l [cm]) by using Equation 1

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

• bioorthogonal reaction (k ≈ 10 M−1s−1) [9] for site-specific labelling or immobilisation of proteins 4, either at an N-terminal cysteine residue or at a 1,2-aminothiol group incorporated into a non-natural amino acid (Scheme 1) [10][11]. In addition, CBT derivatives have been used for the synthesis of polymeric

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

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

• ) bearing either alkyne or azide groups were obtained via acylation of their N-terminal amine by the activated esters method in DMF in the presence of Hünig's base (see Supporting Information File 1 for experimental details). We have pursued several goals: 1) to synthesize a variety of modified MGBs with

• differ in the length and nature of the 3'-linker were synthesized and used for further conjugations [17][30]. Synthesis of polyamide-TFO conjugates by CuAAC reaction To establish conditions for the synthesis of TFO-MGB conjugates we used 5'-alkyne modified parallel TFOs (15–17) in combination with the N

• -terminal azide-modified MGBs 12 and 14 (see Figure 12, Figure 2B for the synthesis and Supporting Information File 1 for experimental details). Three combinations of the components were tried: TFO 15 and MGB 14 resulting in conjugate 23, TFO 16 (bifunctional) + two MGBs 12 (conjugate 24) and TFO 17 + MGB