Polymer degrading marine Microbulbifer bacteria: an un(der)utilized source of chemical and biocatalytic novelty

• Weimao Zhong and
• Vinayak Agarwal

Beilstein J. Org. Chem. 2024, 20, 1635–1651, doi:10.3762/bjoc.20.146

• [48]. The three-dimensional structure of CEST revealed that it belongs to the α/β-class of proteins consisting of a central six-stranded β-sheet flanked by eight α-helices. Site-directed mutagenesis indicated that a Ser-His-Glu catalytic triad was essential for the enzyme activity [48]. Another cold

Identification of the new prenyltransferase Ubi-297 from marine bacteria and elucidation of its substrate specificity

• Jamshid Amiri Moghaddam,
• Huijuan Guo,
• Karsten Willing,
• Thomas Wichard and
• Christine Beemelmanns

Beilstein J. Org. Chem. 2022, 18, 722–731, doi:10.3762/bjoc.18.72

• several transmembrane α-helices and carry a conserved and distinct aspartic-rich Mg2+-binding domain. We heterologously produced UbiA-like Ptases from the bacterial genera Maribacter, Zobellia, and Algoriphagus in Escherichia coli. Investigation of their substrate scope uncovered the preferential

• -297, we performed sequence alignments and structure homology modelling using Swiss-Model (Figure 4) [32], which revealed the transmembrane domain consisting of ten α-helices and loops connecting the transmembrane helices (Figure S2 in Supporting Information File 1), similar to archaeal UbiA

Peptide stapling by late-stage Suzuki–Miyaura cross-coupling

• Hendrik Gruß,
• Rebecca C. Feiner,
• Ridhiwan Mseya,
• David C. Schröder,
• Michał Jewgiński,
• Kristian M. Müller,
• Rafał Latajka,
• Antoine Marion and
• Norbert Sewald

Beilstein J. Org. Chem. 2022, 18, 1–12, doi:10.3762/bjoc.18.1

• P5 successfully quenches such biologically unfavourable conformation and significantly increases the probability of forming helical structures that closely resemble the active conformation of axin’s binding domain. Both, cis and trans isomers form α-helices with a high probability, yet the trans

¹⁹F NMR as a tool in chemical biology

• Diana Gimenez,
• Aoife Phelan,
• Cormac D. Murphy and
• Steven L. Cobb

Beilstein J. Org. Chem. 2021, 17, 293–318, doi:10.3762/bjoc.17.28

• [80]. Previous studies have shown that in the monomeric state the two helical domains of Myc display unstable structural features, similar to those of small IDPs, existing rather as a highly flexible pair of transient α-helices [81]. Based on this, Konrat and co-workers explored a combination of 19F

Current understanding and biotechnological application of the bacterial diterpene synthase CotB2

• Ronja Driller,
• Daniel Garbe,
• Norbert Mehlmer,
• Monika Fuchs,
• Keren Raz,
• Dan Thomas Major,
• Thomas Brück and
• Bernhard Loll

Beilstein J. Org. Chem. 2019, 15, 2355–2368, doi:10.3762/bjoc.15.228

• of CotB2. [36][37][38]. Overall structure of CotB2wt in the open, inactive conformation The structure of CotB2wt (PDB-ID 4OMG [38] and PDB-ID 5GUC [36]) is complete, except for the 15 N-terminal and 12 C-terminal residues. CotB2 consists of ten core α-helices (A to J) that are connected by short loop

• segments and additional five short α-helices (α1 to α5; (Figure 2A and B)). CotB2 resembles the classical α-helical fold of TPSs [18] with significant differences in its primary sequence compared to other TPSs. The core α-helices surround a large, deep cleft, which forms the active site (Figure 2A and B

• differences. The binding of FGGDP and three Mg2+ ions induces a translation and rotation of α-helices B, C, D, F and H towards the active site to accurately position the Asp-rich motif and to subsequently transfer the active site into a product-shaped conformation (Figure 3). Now, a significant change in the

Molecular basis for the plasticity of aromatic prenyltransferases in hapalindole biosynthesis

• Takayoshi Awakawa and
• Ikuro Abe

Beilstein J. Org. Chem. 2019, 15, 1545–1551, doi:10.3762/bjoc.15.157

• amino acid sequence alignment of AmbP1, AmbP3, and other ABBA PTases, visualized by ESPript3 [34]. Secondary structure elements: α, α-helices; β, β-strands; η, 310-helices; TT, strict β-turns. The red frames indicate amino acids that anchor pyrophosphate, the blue frames indicate the residues that

Olefin metathesis catalysts embedded in β-barrel proteins: creating artificial metalloproteins for olefin metathesis

• Daniel F. Sauer,
• Johannes Schiffels,
• Takashi Hayashi,
• Ulrich Schwaneberg and
• Jun Okuda

Beilstein J. Org. Chem. 2018, 14, 2861–2871, doi:10.3762/bjoc.14.265

• olefin metathesis reactions [19]. To date, eight artificial metatheases have been reported. Among them, β-barrel proteins play a central role as protein scaffolds. β-Barrel proteins Proteins are constructed from two major secondary structural elements, namely α-helices and β-sheets. Notably, the latter

• membrane. TIM-barrels (named after triosephosphate isomerase, TIM), in turn, contain both α- and β-structures, i.e., a β-barrel structure (eight strands) enclosed by a series of eight α- helices. The TIM-barrel represents a very common – yet evolutionarily diverse – protein structure [40]. While following

• , the artificial metatheases based on NB4exp were capable of catalyzing both CM and RCM. This makes NB4exp based biohybrid catalysts the first artificial metatheases to catalyze all basic metathesis reactions [62]. For the artificial metathease based on Sav, additional structural motifs – α-helices

Design and biological characterization of novel cell-penetrating peptides preferentially targeting cell nuclei and subnuclear regions

• Anja Gronewold,
• Mareike Horn and
• Ines Neundorf

Beilstein J. Org. Chem. 2018, 14, 1378–1388, doi:10.3762/bjoc.14.116

• trifluoroethanol (TFE) [24]. As can be depicted from Figure 1, all peptides exhibited a random coil structure in phosphate buffer without TFE. In the presence of TFE, the peptides N50 and NrTP also exhibited a random coil structure, whereas N50-sC18* and NrTP-sC18* formed α-helices. This was also confirmed by the

• -sC18* and NrTP-sC18* formed α-helices that showed amphipathic character with a clear hydrophilic and hydrophobic face (Figure 1C). This property might support the interaction with the plasma membrane. Cytotoxic profile of novel CPPs In the next step, the cytotoxicity profiles of the novel peptide

• residues within the sequences. These effects were already described by other groups working with highly cationic CPPs [29][30][31][32]. Moreover, the formation of amphipathic α-helices is often one major factor for efficient peptide/lipid interaction, initiating the following internalization process [33

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

• 0.5 r.m.s.) from exact rotational symmetry. Five long α-helices surround the central cylindrical pore through which the A2-subunit is threaded. Each subunit of a B-pentamer has a single binding site for the GM1 oligosaccharide on the face of the pentamer distal to the A1-subunit [12][14]. GM1 is a

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

G-Protein coupled receptors: answers from simulations

• Timothy Clark

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

• GPCRs. GPCRs consist of seven α-helices that span the membrane between the extra- and intracellular sides. The N-terminus is extracellular and the C-terminus intracellular. The helices are connected by three intracellular loops (IL1, H1-H2; IL2, H3-H4 and IL3, H5-H6) and three extracellular ones (EL1

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

• for analysis (PDB ID: 5EX8; ethylene glycol cryo-protectant solution). The StaF structure is well resolved and adopts the typical structure of a cytochrome P450 [34], which consists predominantly of α-helices (12 in total: labelled A to L, including two additional helices labelled A’ and J’, Figure 5A

• was derived from the StaF crystal structure (PDB ID: 5EX8) and is shown above the alignment (α-helices = blue, β-sheets = magenta). The PRDD-region, which has been shown to be crucial for interaction with the X-domain is highlighted in an orange box. Sequence alignment of the A47934 (sta) and

• teicoplanin (tei) X-domain; secondary structure was derived from the Xtei-OxyBtei complex (PDB ID: 4TX3) and is shown above the alignment (α-helices = blue, β-sheets = magenta); the residues crucial for interaction with cytochrome P450s are shown in orange and both the crossover I region (purple) and 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

• amyloid formation. To ensure the UV-activity of the peptide as analytical tool, Abz (anthranilic acid) was coupled to the N-terminus. The resulting peptide contains elements of α-helices and β-sheets, and a recognition site for PKA. To investigate the structural changes that KFM6 undergoes in the absence

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

• classic aliphatic, hydrophobic interactions, based on the electrostatic component of aromatic interactions. In the late 1980’s and early 1990’s, much work was also done defining the factors that stabilize monomeric α-helices, including the role of noncovalent interactions such as salt bridges, as

• systematic variation and we published several papers using α-helical scaffolds [10][11]. However, one limitation of α-helices is that their folding is not two state, thus requiring indirect methods to measure the influence of a noncovalent interaction on folding. About that time, several papers had been

• attractive scaffold because a two-state approximation for folding was reasonable in most cases and the β-hairpin is far more amenable to NMR analysis than α-helices, which were usually characterized by Circular Dichroism (CD). Additionally, because the sidechains in β-hairpins interdigitate, they provide

Impact of multivalent charge presentation on peptide–nanoparticle aggregation

• Daniel Schöne,
• Boris Schade,
• Christoph Böttcher and
• Beate Koksch

Beilstein J. Org. Chem. 2015, 11, 792–803, doi:10.3762/bjoc.11.89

• ][35][36]. The coiled-coil folding motif consists of two to seven α-helices that are wrapped around each other to form a left-handed supercoil. The primary sequence consists of a regular pattern of seven amino acids denoted with a, b, c, d, e, f, and g, which is referred to as the heptad repeat

• R2A5. CD measurements were carried out at pH 9 and pH 11 at a final peptide concentration of 30 µM (Figure 2A/B). The spectra confirmed that all peptides fold into α-helices as indicated by the two characteristic minima at 208 nm and 222 nm and the maximum at 195 nm. Whereas there are no significant

Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics

• Gijs Koopmanschap,
• Eelco Ruijter and
• Romano V.A. Orru

Beilstein J. Org. Chem. 2014, 10, 544–598, doi:10.3762/bjoc.10.50

• induce secondary structures such as β-turns, β-hairpins in β-sheets and α-helices [141]. Therefore, DKPs are often used as peptidomimetic building blocks. A more detailed review of diketopiperazines is published by Borthwick and Piarulli [141][142]. Standard multicomponent reactions towards DKPs have the

Synthesis of enantiomerically pure (2S,3S)-5,5,5-trifluoroisoleucine and (2R,3S)-5,5,5-trifluoro-allo-isoleucine

• Holger Erdbrink,
• Elisabeth K. Nyakatura,
• Susanne Huhmann,
• Ulla I. M. Gerling,
• Dieter Lentz,
• Beate Koksch and
• Constantin Czekelius

Beilstein J. Org. Chem. 2013, 9, 2009–2014, doi:10.3762/bjoc.9.236

• -CF3 group and the helix. In agreement with these findings, we previously showed that the replacement of a CH3 group by a CF3 substituent in close proximity to the α-carbon of aliphatic amino acids dramatically reduces their α-helix propensity [13]. Since isolated α-helices are only marginally stable

The diketopiperazine-fused tetrahydro-β-carboline scaffold as a model peptidomimetic with an unusual α-turn secondary structure

• Francesco Airaghi,
• Andrea Fiorati,
• Giordano Lesma,
• Manuele Musolino,
• Alessandro Sacchetti and
• Alessandra Silvani

Beilstein J. Org. Chem. 2013, 9, 147–154, doi:10.3762/bjoc.9.17

• proteins can also occur thanks to less common substructures, for example involving five amino acids residues, such as the case of the α-turns. Even if a very large majority of α-turn segments form a part of regular α-helices, isolated α-turns have been reported [35], which are stabilized by a 5→1 hydrogen

Design of a novel tryptophan-rich membrane-active antimicrobial peptide from the membrane-proximal region of the HIV glycoprotein, gp41

• Evan F. Haney,
• Leonard T. Nguyen,
• David J. Schibli and
• Hans J. Vogel

Beilstein J. Org. Chem. 2012, 8, 1172–1184, doi:10.3762/bjoc.8.130

• ]. This binding event is integral to the mechanism of action of the peptide, either through direct damage to the phospholipid bilayer or by allowing the peptide to cross the bacterial membrane to reach intracellular targets [2]. A number of AMPs form amphipathic α-helices when bound to lipid bilayers with

• are unstructured in solution, and they adopt amphipathic α-helices when bound to a phospholipid bilayer [3][23]. This binding to the bacterial membrane is often related to a membrane-destabilizing mode of action, which ultimately leads to bacterial cell death [24]. However, recent evidence suggests

Parallel solid-phase synthesis of diaryltriazoles

• Matthias Wrobel,
• Jeffrey Aubé and
• Burkhard König

Beilstein J. Org. Chem. 2012, 8, 1027–1036, doi:10.3762/bjoc.8.115

• acids in proteins being part of α-helices [2], it is the most common secondary structure found in proteins [3]. Protein–protein as well as protein–DNA and protein–RNA interactions often involve α-helices as recognition motifs on protein surfaces [4]. These helices are important targets for new drugs

Investigation of the network of preferred interactions in an artificial coiled-coil association using the peptide array technique

• Raheleh Rezaei Araghi,
• Carsten C. Mahrenholz,
• Rudolf Volkmer and
• Beate Koksch

Beilstein J. Org. Chem. 2012, 8, 640–649, doi:10.3762/bjoc.8.71

• denaturation. Keywords: β- and γ-amino acids; coiled coil; foldamer; screening libraries; SPOT technique; Introduction Coiled-coil domains, which consist of two or more α-helices, are the most common representatives of α-helix-mediated protein–protein interactions, which regulate many important biological

Synthesis of new C^α-tetrasubstituted α-amino acids

• Andreas A. Grauer and
• Burkhard König

Beilstein J. Org. Chem. 2009, 5, No. 5, doi:10.3762/bjoc.5.5

• -turns [6], or 310- or α-helices [7][8][9][10][11]. Cα-Tetrasubstituted α-amino acids are therefore of importance for the synthesis of peptides or peptidomimetics with properties such as increased chemical and metabolic stability, increased hydrophobicity, or increased conformational constraints [12][13

Colchitaxel, a coupled compound made from microtubule inhibitors colchicine and paclitaxel

• Karunananda Bombuwala,
• Thomas Kinstle,
• Vladimir Popik,
• Sonal O. Uppal,
• James B. Olesen,
• Jose Viña and
• Carol A. Heckman

Beilstein J. Org. Chem. 2006, 2, No. 13, doi:10.1186/1860-5397-2-13

• residue 205, forms a Rossmann fold in which parallel β-strands alternate with four α-helices. The next domain contains five helices and a mixed β-sheet, one strand of which is contiguous to the β-sheet in the amino-terminal domain. Nogales and coworkers showed that the α-subunit resembles the β- and is