Phenanthridine–pyrene conjugates as fluorescent probes for DNA/RNA and an inactive mutant of dipeptidyl peptidase enzyme

• Josipa Matić,
• Tana Tandarić,
• Marijana Radić Stojković,
• Filip Šupljika,
• Zrinka Karačić,
• Ana Tomašić Paić,
• Lucija Horvat,
• Robert Vianello and
• Lidija-Marija Tumir

Beilstein J. Org. Chem. 2023, 19, 550–565, doi:10.3762/bjoc.19.40

• and Phen-Py-2 with biomolecules Conjugates Phen-Py-1 and Phen-Py-2 were examined for DNA/RNA binding affinity and eventual preference for different polynucleotide structures. For example, the B-helical structure had a well-defined minor groove which is suitable for minor groove binding, while A

• -helical structure is favorable for intercalation and/or major groove binding. Calf thymus DNA (ct-DNA, 58% AT and 42% GC base pairs) and poly rA–poly rU (RNA) were chosen as models for a classical B-helical and A-helical structure, respectively [35]. Unlike Phen-Py-2, compound Phen-Py-1 showed notable

Selected peptide-based fluorescent probes for biological applications

• Debabrata Maity

Beilstein J. Org. Chem. 2020, 16, 2971–2982, doi:10.3762/bjoc.16.247

• 4 binds with dsDNA in a combined intercalation and minor groove binding mode, whereas probe 5 binds with the outer surface of dsDNA. These two probes are low cytotoxic and probe 4 has been successfully used for imaging of nuclear DNA (Figure 5B, inset). Protein detection Specific peptides and

Naphthalene diimide bis-guanidinio-carbonyl-pyrrole as a pH-switchable threading DNA intercalator

• Poulami Jana,
• Filip Šupljika,
• Carsten Schmuck and
• Ivo Piantanida

Beilstein J. Org. Chem. 2020, 16, 2201–2211, doi:10.3762/bjoc.16.185

• -DNAs only at pH 5, while at neutral conditions (pH 7) NDI-GCP2 switched to the DNA minor groove binding. Intriguingly, NDI-GCP2 was at both pH values studied bound to the ds-RNA major groove, still showing a higher affinity and thermal denaturation effect at pH 5 due to GCP protonation. At excess over

• threading intercalation into ds-DNAs at pH 5, while compound 4 at neutral conditions (pH 7) switched to the DNA minor groove binding. As often observed for threading intercalators, compound 4 was selective toward GC-DNA. Intriguingly, compound 4 was at both pH values bound to the ds-RNA major groove, most

Naphthalene diimide–amino acid conjugates as novel fluorimetric and CD probes for differentiation between ds-DNA and ds-RNA

• Annike Weißenstein,
• Myroslav O. Vysotsky,
• Ivo Piantanida and
• Frank Würthner

Beilstein J. Org. Chem. 2020, 16, 2032–2045, doi:10.3762/bjoc.16.170

• peptide chain and DNA/RNA interacting aromatic moiety, for instance peptide-based DNA/RNA-intercalators [1][2], as well as many DNA/RNA groove binding small molecules [3][4]. Inspired by these natural examples, the development of novel DNA/RNA targeting synthetic molecules has been in scientific focus for

• several decades, consequently becoming increasingly complex [5][6][7]. This includes examples incorporating several types of non-covalent interaction with DNA/RNA (intercalation, groove binding, positive–negative charge interaction [5][8]) in one molecule or even modified biomacromolecules (e.g., proteins

Reversible photoswitching of the DNA-binding properties of styrylquinolizinium derivatives through photochromic [2 + 2] cycloaddition and cycloreversion

• Sarah Kölsch,
• Heiko Ihmels,
• Jochen Mattay,
• Norbert Sewald and
• Brian O. Patrick

Beilstein J. Org. Chem. 2020, 16, 111–124, doi:10.3762/bjoc.16.13

• could be deduced. With increasing LDR, however, another binding mode became predominant for the ligands 3a–c, as particularly indicated by the development of a positive LD band in the absorption range of the ligand that denoted groove binding [74][75][76]. It is proposed that with increasing ligand

Photocontrolled DNA minor groove interactions of imidazole/pyrrole polyamides

• Sabrina Müller,
• Jannik Paulus,
• Jochen Mattay,
• Heiko Ihmels,
• Veronica I. Dodero and
• Norbert Sewald

Beilstein J. Org. Chem. 2020, 16, 60–70, doi:10.3762/bjoc.16.8

• compounds have frequently been employed as modules, e.g., to control protein–DNA interactions. However, their use in conjunction with minor groove-binding imidazole/pyrrole (Im/Py) polyamides is yet unprecedented. Dervan-type Im/Py polyamides were equipped with an azobenzene unit, i.e., 3-(3-(aminomethyl

• )phenyl)azophenylacetic acid, as the linker between two Im/Py polyamide strands. Only the (Z)-azobenzene-containing polyamides bound to the minor groove of double-stranded DNA hairpins. Photoisomerization was exemplarily evaluated by 1H NMR experiments, while minor groove binding of the (Z)-azobenzene

• acted as a building block inducing a reverse turn, which favored hydrogen bonds between the pyrrole/imidazole amide and the DNA bases. In contrast, the E-configured polyamides did not induce any ICD characteristic for minor groove binding. The incorporation of the photoswitchable azobenzene unit is a

Identification of optimal fluorescent probes for G-quadruplex nucleic acids through systematic exploration of mono- and distyryl dye libraries

• Xiao Xie,
• Michela Zuffo,
• Marie-Paule Teulade-Fichou and
• Anton Granzhan

Beilstein J. Org. Chem. 2019, 15, 1872–1889, doi:10.3762/bjoc.15.183

• the mono-styryl dye family, in the presence of G4-DNA has been reported earlier this year [49]. Moreover, mono-styryls 17a and 18a (the latter also known as DASPMI) are long-known and widely used as mitochondrial stains [87][88] and groove-binding fluorescent probes for double-stranded DNA [89][90

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

• particular, we cover the advances made in DNA minor groove recognition using new analogues and derivatives of classical minor groove binders such as distamycin, netropsin, polyamides, bisbenzimidazoles and organic cations. We have also included new intercalating agents as well as major groove binding ligands

• all DNA binding agents, this review article intends to provide a substantial coverage of new advancements made in the discovery of major leads in three most visited areas (groove recognition, intercalation and cross linking agents) of DNA recognition. 2. Minor groove binders (MGBs) DNA groove binding

• . However, these energetic costs are balanced and outweighed by favorable contributions from the hydrophobic transfer of drugs from solution to DNA-binding site [28][29]. Groove binding usually does not influence huge structural/conformational changes in the DNA duplex; this mode of binding may be

Fluorogenic PNA probes

• Tirayut Vilaivan

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

• duplexes by various mechanisms, such as groove binding or intercalation. This fluorescent label may be a stand-alone entity (referred to as a tethered label) or combined with a nucleobase that integrates the base pairing and the fluorescence sensing in a single event. The latter strategy should allow a

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

• between nucleic acids and small ligands. This tutorial aims to help researchers entering the research field to organize experiments accurately and to interpret the obtained data reliably. Keywords: circular dichroism; emission-based dichroism; groove binding; intercalation; linear dichroism; non-covalent

• . Among the methods discussed, primary focus will be centered on the most frequently employed techniques, ECD and LD. Moreover, we will elaborate the interpretation of results not only for the most common DNA, RNA/ligand binding modes (intercalation, groove binding) but also for increasingly appearing

• range indicates a disruption of helical chirality by intercalation or severe kinking of the helix by sterically demanding groove binders. At variance, if the ECD spectrum of the DNA and RNA does not change significantly, the biopolymer helical structure is preserved, suggesting a ligand groove binding

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

• improved synthetic approaches. Keywords: ds-DNA and ds-RNA binding; intercalation; minor groove binding; nucleic acids; organic synthesis; phenanthridine; phenanthridinium; Introduction The search for therapeutic agents of the phenanthridine type has increased when the outstanding trypanocidal activity

• between various DNA and RNA polynucleotides was attributed to the switch of the binding mode (intercalation into dGdC-DNA and AU-RNA and minor groove binding into dAdT-DNA). A common strategy for the modification of DNA- and RNA-targeting molecules by preparation of homo-dimers was also implemented on the

• interactions between two phenanthridinium subunits and consequently their DNA- and RNA-binding mode (shorter linker–minor groove binding, the longest linker–intercalation) [66][67]. In addition, the derivative with the longest linker was, to the best of our knowledge, the first bis-phenanthridine-based

Autonomous assembly of synthetic oligonucleotides built from an expanded DNA alphabet. Total synthesis of a gene encoding kanamycin resistance

• Kristen K. Merritt,
• Kevin M. Bradley,
• Daniel Hutter,
• Mariko F. Matsuura,
• Diane J. Rowold and
• Steven A. Benner

Beilstein J. Org. Chem. 2014, 10, 2348–2360, doi:10.3762/bjoc.10.245

• –Crick interactions (e.g., wobble, major groove binding) can also compete with Watson–Crickery (Figure 1). The work reported here began with the observation that several of the structural features of DNA that intrinsically limit autonomous assembly of standard DNA fragments might be overcome by adding

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

• recognition; circular dichroism; DBTAA-adenine conjugate; ds-DNA/RNA; minor groove binding; nucleic acids; Introduction The majority of natural and artificial applications involving small molecule-DNA/RNA recognition depend on several non-covalent binding modes. Typical examples are double-stranded (ds) DNA

• /RNA intercalation, minor or major groove binding, and external electrostatic binding [1]. However, non-covalent interactions involving small molecules (Mw < 600) can only rely on a small number of interacting groups, while the steric parameters of DNA/RNA binding sites are also quite limited

• many groove binding molecules. The inability of the entire AP series to stabilize ds-DNA/RNA (Table 1), in combination with a considerable binding affinity (Table 2) gives rise to the question of the AP series binding mode. To shed more light on the unusual binding process of the AP dyes, it was

Synthesis and optical properties of pyrrolidinyl peptide nucleic acid carrying a clicked Nile red label

• Nattawut Yotapan,
• Chayan Charoenpakdee,
• Pawinee Wathanathavorn,
• Boonsong Ditmangklo,
• Hans-Achim Wagenknecht and
• Tirayut Vilaivan

Beilstein J. Org. Chem. 2014, 10, 2166–2174, doi:10.3762/bjoc.10.224

• increase in the fluorescence quantum yield upon hybridization with complementary DNA irrespective of the nature of the flanking bases. In such duplexes, the Nile red is expected to interact with the PNA–DNA duplexes by means of groove binding, which results in a lower localized polarity around the Nile red

OligArch: A software tool to allow artificially expanded genetic information systems (AEGIS) to guide the autonomous self-assembly of long DNA constructs from multiple DNA single strands

• Kevin M. Bradley and
• Steven A. Benner

Beilstein J. Org. Chem. 2014, 10, 1826–1833, doi:10.3762/bjoc.10.192

• give single-strand structures (such as hairpins), this unimolecular process competes with intermolecular duplex formation. Finally, a rich repertoire of non-Watson–Crick interactions (e.g., wobble, major groove binding) can compete with Watson–Crickery (Figure 1) to render autonomous self-assembly

(Pseudo)amide-linked oligosaccharide mimetics: molecular recognition and supramolecular properties

• José L. Jiménez Blanco,
• Fernando Ortega-Caballero,
• Carmen Ortiz Mellet and
• José M. García Fernández

Beilstein J. Org. Chem. 2010, 6, No. 20, doi:10.3762/bjoc.6.20

• studies showed that hybridization of DNG-Hoechst conjugates 64 and 65 to dsDNA enhances the stability of the triple helix through simultaneous minor groove binding by the tethered Hoechst 33258 ligand. Furthermore, Hoechst 33258 is able to enhance the stability of the duplex DNG·DNA with a flexible minor