Polarization spectroscopy methods in the determination of interactions of small molecules with nucleic acids – tutorial

• Tamara Šmidlehner,
• Ivo Piantanida and
• Gennaro Pescitelli

Beilstein J. Org. Chem. 2018, 14, 84–105, doi:10.3762/bjoc.14.5

• the wavelength range where DNA and RNA absorb light (λ = 200–300 nm) and thus possess intrinsic spectra. Changes in the intrinsic spectral properties of DNA or RNA can often be correlated to a specific change in the secondary structure of the polynucleotide (see chapter 2.1.). However, if a ligand’s

• adequately prepared and characterized. For that reason, a short description of the most important issues in sample preparation is summarized in chapters 2.2 and 2.3. 2.1. Relation between DNA or RNA secondary structure and polarization spectroscopy Nucleobases are achiral but nucleoside and nucleotide

• mechanism between the various π→π* transitions of regularly arranged chromophores [14] (Figure 3, top). Chiroptical properties and ECD spectra of particular DNA or RNA sequences are therefore strongly dependent on the polynucleotide secondary structure [15], at variance to the common UV–vis spectra of the

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

• fluorinated GLP-1 analogues displayed higher proteolytic stability against this enzyme [27]. Usually, the enhanced proteolytic stability of fluorinated peptides is explained by their greater hydrophobicity and altered secondary structure compared to the parent, non-fluorinated peptide. A further reason is 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

• important for the activity (Table 6). Conformational studies of the fluorinated peptide using circular dichroism also showed that the incorporation of the monofluoroalkene did not perturb the formation of the secondary structure of the peptide, which was a α-helix. Dory and co-workers wanted to study the

Homologated amino acids with three vicinal fluorines positioned along the backbone: development of a stereoselective synthesis

• Raju Cheerlavancha,
• Ahmed Ahmed,
• Yun Cheuk Leung,
• Aggie Lawer,
• Qing-Quan Liu,
• Marina Cagnes,
• Hee-Chan Jang,
• Xiang-Guo Hu and
• Luke Hunter

Beilstein J. Org. Chem. 2017, 13, 2316–2325, doi:10.3762/bjoc.13.228

• affect the secondary structure of peptides within which they are contained, with consequent implications for the peptides’ biological potency and selectivity [1]. A more subtle example of this concept is provided by the amino acid β-methylphenylalanine (2), which exerts conformational bias through

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

• 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

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

• cyan/ blue; PDB ID: 4TX3); (D) an overlay of StaF (orange) on the structure of OxyAtei (yellow) showing the location of the N-terminal regions of other molecules within the crystal lattice for both StaF (purple) and OxyAtei (green). Sequence alignment of StaF and OxyAtei. Protein secondary structure

• 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

Interactions between cyclodextrins and cellular components: Towards greener medical applications?

• Loïc Leclercq

Beilstein J. Org. Chem. 2016, 12, 2644–2662, doi:10.3762/bjoc.12.261

• described locally by their secondary and tertiary structures. The secondary structure describes the arrangement of amino acid residues observed at the atomic scale stabilized mainly by H-bonds (e.g., α-helix, β-sheet and turns). The tertiary structure corresponds to the general shape of the observable

• protein across the whole molecule. It describes the interactions between the different elements of the secondary structure. Finally, the assembly of several protein subunits to form a functional complex is described by the quaternary structure [54]. As some amino acids have hydrophobic side chains (e.g

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

• -terminus to have a stabilizing effect on the original secondary structure [55], we demonstrate that phosphorylation proximal to the C-terminus can also significantly inhibit amyloid formation. Delayed ATP or PKA addition lead in all cases to a stop of the amyloid formation and to stabilization of remaining

• solubility of the peptide. Calculated secondary structure propensities, using the TANGO algorithm, identify a nine amino acid long β-aggregation domain (E-L-V-V-L-K-S-E-L-) for KFM6 (Supporting Information File 1, Figure S5). Those aggregation domains are found in almost every peptide with the propensity to

Supramolecular chemistry: from aromatic foldamers to solution-phase supramolecular organic frameworks

• Zhan-Ting Li

Beilstein J. Org. Chem. 2015, 11, 2057–2071, doi:10.3762/bjoc.11.222

• in acetonitrile. Upon oxidation of the TTF units to radical cation TTF·+, the polymers adopted flexible conformations. When the viologen units were reduced to radical cations, the radical cations stacked intramolecularly to induce the backbone to form another kind of pleated secondary structure

Synthesis of constrained analogues of tryptophan

• Elisabetta Rossi,
• Valentina Pirovano,
• Marco Negrato,
• Giorgio Abbiati and
• Monica Dell’Acqua

Beilstein J. Org. Chem. 2015, 11, 1997–2006, doi:10.3762/bjoc.11.216

• framework in a cyclic or bicyclic structure confers specific features to the synthesized molecules: well-defined secondary structure, structural rigidity, enhanced binding activity and selectivity [6][7]. For example, bupivacaine (Figure 1), commercialized by Sanofi, is a local anesthetic drug containing a

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

• result in any changes in the CD spectra, indicating that there is no concentration-dependent change in the secondary structure of the peptides. At pH 11 the CD spectra of all peptides are virtually identical and indicate the presence of α-helical coiled-coil structures. Dynamic light scattering (DLS) was

• later on proven by the lack of changes in the secondary structure of peptide R1A3. Accordingly, an increase in the number of arginine residues at f-positions to two in case of R2A2 leads to a significant shift of the LSPR band of 1.20 to 3.75 nm (Figure 4D). As shown in Figure 4D, these red-shifts

• even after three days the value is only half of those measured for R2A3 and R2A4. It is known that gold nanoparticles may affect the secondary structure of a peptide or protein [33]. To investigate the effect of Au/MUA nanoparticles on the secondary structure of the peptides included in this study, CD

The Shono-type electroorganic oxidation of unfunctionalised amides. Carbon–carbon bond formation via electrogenerated N-acyliminium ions

• Alan M. Jones and
• Craig E. Banks

Beilstein J. Org. Chem. 2014, 10, 3056–3072, doi:10.3762/bjoc.10.323

• a linear peptide sequence was accomplished using an anodic oxidation step (Scheme 21). The stabilisation of linear peptides via inducing a stabilised secondary structure is of importance in mimicking protein–protein interactions (PPI) for diseases such as cancer and HIV [89][90]. The methoxylated

First chemoenzymatic stereodivergent synthesis of both enantiomers of promethazine and ethopropazine

• Paweł Borowiecki,
• Daniel Paprocki and
• Maciej Dranka

Beilstein J. Org. Chem. 2014, 10, 3038–3055, doi:10.3762/bjoc.10.322

• its secondary structure mainly by stabilization of the internal hydrogen-bonding network in the molecule, thus improving the reactivity and selectivity of organic substrate transformations. Therefore, an appropriate medium selection in which a relatively high solubility of the phenothiazinic substrate

Come-back of phenanthridine and phenanthridinium derivatives in the 21st century

• Lidija-Marija Tumir,
• Marijana Radić Stojković and
• Ivo Piantanida

Beilstein J. Org. Chem. 2014, 10, 2930–2954, doi:10.3762/bjoc.10.312

• the thermal denaturation and ICD signal-based sensing was highly sensitive to the polynucleotide basepair composition and secondary structure [76]. However, the low solubility of the studied systems hampered NMR studies and the very complex set of possible interactions did not allow accurate

Stereoselective synthesis of perillaldehyde-based chiral β-amino acid derivatives through conjugate addition of lithium amides

• Zsolt Szakonyi,
• Reijo Sillanpää and
• Ferenc Fülöp

Beilstein J. Org. Chem. 2014, 10, 2738–2742, doi:10.3762/bjoc.10.289

• secondary structure of foldamers, the introduction of well-designed hydrophilic or hydrophobic substituents on the alicyclic ring of β-amino acids can modify the fine structure of β-peptides. There are several powerful synthetic methods through which alicyclic or bicyclic β-amino acid enantiomers can be

Molecular recognition of AT-DNA sequences by the induced CD pattern of dibenzotetraaza[14]annulene (DBTAA)–adenine derivatives

• Marijana Radić Stojković,
• Marko Škugor,
• Łukasz Dudek,
• Jarosław Grolik,
• Julita Eilmes and
• Ivo Piantanida

Beilstein J. Org. Chem. 2014, 10, 2175–2185, doi:10.3762/bjoc.10.225

• , Supporting Information File 1). The choice of long polynucleotides ensures that significant binding of the DBTAA moiety at the ends of the double strands (“capping”) can be neglected and that our investigations indeed sense the differences of the secondary structure (from minor/major groove) of the studied

• interactions. The polynucleotide secondary structure is chiral itself, and any binding-induced conformational changes are reflected in the CD spectrum [19]. Moreover, the uniform binding of achiral small molecules within chiral DNA/RNA helix results in an induced CD spectrum (ICD) of the small molecule

• DBTAA chromophore within the DNA groove [20]. A more detailed analysis of ICD data revealed that ICD bands of AP3/AP3am were highly sensitive to the secondary structure of DNA/RNA and, in particular, the minor groove properties (Table S1, Supporting Information File 1). For instance, the ICD bands of

Convergent synthetic methodology for the construction of self-adjuvanting lipopeptide vaccines using a novel carbohydrate scaffold

• Vincent Fagan,
• Istvan Toth and
• Pavla Simerska

Beilstein J. Org. Chem. 2014, 10, 1741–1748, doi:10.3762/bjoc.10.181

• wider application for the convenient acylation of Fmoc-lysine. Synthesis of azide functionalized J8 B cell epitope (N3-J8) The conserved C-terminal region of the M protein adopts an α-helical secondary structure [13]. In order to maintain this native secondary structure, the J8 epitope (QAEDKVKQ

Synthesis of the first examples of iminosugar clusters based on cyclopeptoid cores

• Mathieu L. Lepage,
• Alessandra Meli,
• Anne Bodlenner,
• Céline Tarnus,
• Francesco De Riccardis,
• Irene Izzo and
• Philippe Compain

Beilstein J. Org. Chem. 2014, 10, 1406–1412, doi:10.3762/bjoc.10.144

• bonds, which can isomerize more readily than secondary amides, and to the absence of amide protons, which stabilize secondary structure by backbone hydrogen bonding [15][16]. As we have previousy demonstrated, this heterogeneity can be reduced by metal chelation [35][38]. Addition of an excess of sodium

A new building block for DNA network formation by self-assembly and polymerase chain reaction

• Holger Bußkamp,
• Sascha Keller,
• Marta Robotta,
• Malte Drescher and
• Andreas Marx

Beilstein J. Org. Chem. 2014, 10, 1037–1046, doi:10.3762/bjoc.10.104

• hydrogels. Keywords: AFM; branched DNA; DNA; DNA polymerase; nanotechnology; nucleic acids; PCR; self-assembly; Introduction DNA has found applications in the field of nanotechnology due to its inherent properties. The simplicity and predictability of DNA secondary structure are of outstanding potential

Molecular architecture with carbohydrate functionalized β-peptides adopting 3₁₄-helical conformation

• Nitin J. Pawar,
• Navdeep S. Sidhu,
• George M. Sheldrick,
• Dilip D. Dhavale and
• Ulf Diederichsen

Beilstein J. Org. Chem. 2014, 10, 948–955, doi:10.3762/bjoc.10.93

• oligomers varying the sugar (glucose, galactose, xylose) and sugar protecting groups. The influence of sugar units and the configuration of sugar-β-amino acids on β-peptide secondary structure were investigated by CD spectroscopy. Keywords: carbohydrate recognition; conformation; glycopeptide; β-peptide

• -peptides are especially of interest as peptidomimetic foldamers wherein the presence of β-amino acids rendered them to adopt a variety of conformational stable secondary structures, even with short peptide sequences [4][5][6]. Amongst them the 314-helix is the most significant helical secondary structure

• unprotected β-glycopeptides since the equilibrium between hemiacetal and open-chain aldehyde form also does not interfere with the 314-helix secondary structure and allows further functionalization with saccharides, e.g., by reductive amination. Sketch of right-handed β-peptide helix functionalized in every

Conformation of dehydropentapeptides containing four achiral amino acid residues – controlling the role of L-valine

• Michał Jewgiński,
• Joanna Krzciuk-Gula,
• Maciej Makowski,
• Rafał Latajka and
• Paweł Kafarski

Beilstein J. Org. Chem. 2014, 10, 660–666, doi:10.3762/bjoc.10.58

• secondary structure of peptides is discussed. The obtained results suggest that the strongest influence on the conformation of peptides arises from a valine residue inserted at the C-terminal position. The most ordered conformation was found for peptide Boc-Gly-ΔAla-Gly-ΔZPhe-Val-OMe (3), which adopts a

• important issue of the determination of the secondary structure and properties of peptides is the Z/E-isomerism of dehydroamino acids. This phenomenon can be critical for their biological activity [16][17][18] and for the secondary structure of the peptide chain. Generally, the (Z)-isomers are

• residues and one ΔZPhe residue [28]. These publications show the crucial role of a L-Val present in the N- or C-terminal position for the forming of a secondary structure. To the best of our knowledge, there is no publication on the conformational preference of dehydropeptides containing both

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

• flexibility of the peptide enhancing often affinity for a certain receptor. Moreover, these cyclic mimics force the molecule into a well-defined secondary structure. Constraint structural and conformational features are often found in biological active peptides. For the synthesis of cyclic constrained

• constraints is that they force the molecule into a well-defined secondary structure. Such structural features are often found in biologically active peptides and proteins [8]. Mimicking the secondary structure is of high interest since these motifs are regularly located at the surface of peptide–peptide

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

• their intrinsic tendency to adopt this secondary structure (i.e. their α-helix propensity) was shown to be considerably reduced when compared to their canonical analogues [8][9]. Thus, if enhanced thermal stabilities of helical assemblies containing aliphatic fluorinated building blocks have been

• be essential factors for secondary structure formation, we compared 5-F3Ile with previously studied (2S,3S)-4’-F3Ile [13], as well as with (S)-5,5,5,5’,5’,5’-hexafluoroleucine (F6Leu), which was prepared according to procedures reported by Keese and coworkers [25]. By plotting their side chain van

C–C Bond formation catalyzed by natural gelatin and collagen proteins

• Dennis Kühbeck,
• Basab Bijayi Dhar,
• Eva-Maria Schön,
• Carlos Cativiela,
• Vicente Gotor-Fernández and
• David Díaz Díaz

Beilstein J. Org. Chem. 2013, 9, 1111–1118, doi:10.3762/bjoc.9.123

• secondary structure, HPLC analysis of the reaction mixtures revealed negligible enantioselectivity. This lack of selectivity is in agreement with previous publications dealing with other biocatalysts used in the Henry (nitroaldol) reaction [11][12][13][14][15][16]. At this point, and in order to draw a

A peptidic hydrogel that may behave as a “Trojan Horse”

• Nicola Castellucci,
• Giorgio Sartor,
• Natalia Calonghi,
• Carola Parolin,
• Giuseppe Falini and
• Claudia Tomasini

Beilstein J. Org. Chem. 2013, 9, 417–424, doi:10.3762/bjoc.9.44

• , must occur [3]. The general mechanism of this uptake remains elusive and appears to be unrelated to the presence of specific receptors on the membrane surface or even receptor binding [4]. The peptide secondary structure is very important, as usually the α-helix conformation interacts more easily with