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

• a pH-dependent excimer formation that is significantly red-shifted relative to the pyrene and phenanthridine fluorescence. While the conjugate with a short linker showed negligible spectrophotometric changes due to the polynucleotide addition, the conjugate with a longer and more flexible linker

• in the cell membrane. Keywords: dipeptidyl peptidase enzyme; excimer; molecular dynamics simulations; phenanthridine; polynucleotide; pyrene; Introduction The design of small molecules that can selectively bind and discriminate different biomolecular structures (polynucleotides vs proteins, DNA or

• , and polynucleotide binding affinity has been investigated by UV–vis, fluorescence and CD spectroscopy and molecular modeling. Further, binding of Phen-Py-1 to human dipeptidyl peptidase III enzyme was investigated by fluorescence spectroscopy and microcalorimetric measurements. Results and Discussion

Selected peptide-based fluorescent probes for biological applications

• Debabrata Maity

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

• -polyU) (log K = 3.8 and log K = 4.4 respectively for 4 and 5). Significant differential fluorescence responses of these probes with nucleic acids are due to the positioning of fluorophores within the polynucleotide binding site. Different studies explain their different mode of binding with dsDNA. Probe

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

• the DNA/RNA conjugate NDI-GCP2 showed also aggregation along the ds-polynucleotide and AFM and DLS demonstrated that NDI-GCP2 has pronounced ds-DNA condensation ability. Keywords: AFM; circular dichroism; DNA/RNA recognition; fluorescence; guanidinio-carbonyl-pyrrole; naphthalene diimide

• major groove; in that way allowing two GCP units different recognition environment and therefore eventually better sensing of ds-polynucleotide secondary structures. However, if for some particular ds-DNA or ds-RNA threading intercalation is hampered, such novel NDI-(GCP)2 conjugate (4; Scheme 1) will

• balanced ratio of GC-(48%) and AT-(52%) base pairs, as well as synthetic alternating polynucleotide poly(dAdT)2 with also B-helix structure but with a fully available minor groove for small molecule binding. As alternative we used poly(dGdC)2 differing significantly in the secondary structure as well as in

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

• the type of polynucleotide, thus the studied NDI dyes act as dual fluorimetric/ICD probes for sensing the difference between here used GC-DNA, AT-DNA and AU-RNA. Keywords: amino acid–fluorophore conjugate; circular dichroism; DNA/RNA recognition; fluorescence; intercalation; naphthalene diimide

• dyes by its ability to intercalate into ds-DNA/RNA by “threading” through the polynucleotide double helix [21][22]. Such “threading intercalation” indicates that a large aromatic moiety with bulky groups at opposite ends is inserted between two DNA or RNA base pairs, whereby bulky substituents end in

• both, the minor and major groove of the polynucleotide. Such bulky groups positioning requires the DNA double helix to shortly open at a binding site and close upon threading intercalator insertion. Also, the chosen NDI chromophore is characterised by easily tuneable emission wavelengths [23], and

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

• approach as it monitors changes of only one species involved in the complex formation and thus the interpretation of results is simple and straightforward. However, to design the polarization spectroscopy experiment accurately, it is essential that solutions of both the polynucleotide and the ligand are

• 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

Binding abilities of polyaminocyclodextrins: polarimetric investigations and biological assays

• Marco Russo,
• Daniele La Corte,
• Annalisa Pisciotta,
• Serena Riela,
• Rosa Alduina and
• Paolo Lo Meo

Beilstein J. Org. Chem. 2017, 13, 2751–2763, doi:10.3762/bjoc.13.271

• of a polynucleotide (interacting with the polycationic branches) and a further bioactive/drug molecule (included into the host cavity). The critical examination of the available literature suggests that one main drawback of this approach is the fact that the syntheses of the tailored macrocyclic

• binding are summarized in Table 2. Differences in the apparent binding abilities of AmCDs towards pDNA may depend upon several factors affecting their mutual interaction, i.e., the state of charge, average number and length of polyamine arms of AmCDs, and the intrinsic flexibility of the polynucleotide

Chemical systems, chemical contiguity and the emergence of life

• Terrence P. Kee and
• Pierre-Alain Monnard

Beilstein J. Org. Chem. 2017, 13, 1551–1563, doi:10.3762/bjoc.13.155

• octadecenoic acid (oleic acid) using polynucleotide phosphorylase (PNPase, whose activity under normal conditions leads to RNA degradation, but in the presence of ribonucleotide diphosphates, NDPs, can polymerize random RNA strands) [83] and Q-beta replicase [88]. In the PNPase experiments, the selective

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

• /RNA binding sites allowed H-bonding-based recognition of some complementary polynucleotide sequences. However, the recognition pattern was not straight-forward; for instance N5-protonated phenanthridinium–adenine derivative 12 successfully recognized a complementary poly(U) sequence [72] (Scheme 23

• 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

• allows the incorporation of considerably long substituents at 3,8- positions available for attachment to DNA and RNA and/or various additional non-covalent interactions with the polynucleotide backbone. The ethidium bromide incorporated as an artificial DNA base (18, Figure 9) at specific sites in duplex

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

• ]). Namely, parameters such as the groove width and depth, steric obstructions like the amino groups of guanine, H-bonding patterns, as well as polynucleotide charge density and the curvature of the ds-helix backbone all differ significantly across the double stranded examples mentioned above (Table S1

• affinity determination Titration of the AP series with any studied polynucleotide resulted in a pronounced decrease of the UV–vis absorbance of the DBTAA chromophore at >300 nm (Figure 1, Table 2). However, no measurable shifts of the UV–vis absorption maxima for any of the AP series were observed. In

• necessary to assess the structure of the AP dye/polynucleotide complex. Application of the most informative methods like NMR and X-ray crystallography was hampered by the tendency of the AP dye/DNA complexes to form colloidal systems at c > 0.1 mM, which neither crystalized nor were suitable for NMR studies

Synthesis of a bifunctional cytidine derivative and its conjugation to RNA for in vitro selection of a cytidine deaminase ribozyme

• Nico Rublack and
• Sabine Müller

Beilstein J. Org. Chem. 2014, 10, 1906–1913, doi:10.3762/bjoc.10.198

• reactant merely to the 5'-terminus of library RNAs [15][16][17]. Alternatively, post-transcriptional protocols can address both the 5'- and the 3'-terminus. In general, post-transcriptional 5'-modification may be achieved by thiophosphorylation with T4-polynucleotide kinase followed by derivatization of