Flexibility and Preorganization of Fluorescent Nucleobase-Pyrene Conjugates Control DNA and RNA Recognition

Abstract

We synthesized a new amino acid-fluorescent nucleobase derivative (qAN1-AA) and from it two new fluorescent nucleobase–fluorophore (pyrene) conjugates, whereby only the analogue with the longer and more flexible linker (qAN1-pyr2) self-folded into intramolecularly stacked qAN1/pyrene conformation, yielding characteristic, 100 nm-red-shifted emission (λmax = 500 nm). On the contrary, the shorter and more rigid linker resulted in non-stacked conformation (qAN1-pyr1), characterized by the emission of free pyrene at λmax = 400 nm. Both fluorescent nucleobase–fluorophore (pyrene) conjugates strongly interacted with ds-DNA/RNA grooves with similar affinity but opposite fluorescence response (due to pre-organization), whereas the amino acid-fluorescent base derivative (qAN1-AA) was inactive. However, only intramolecularly self-folded qAN1-pyr2 showed strong fluorescence selectivity toward poly U (Watson–Crick complementary to qAN1 nucleobase) and poly A (reverse Hoogsteen complementary to qAN1 nucleobase), while an opposite emission change was observed for non-complementary poly G and poly C. Non-folded analogue (qAN1-pyr1) showed no ss-RNA selectivity, demonstrating the importance of nucleobase-fluorophore pre-organization.

Triarylborane Dyes as a Novel Non-Covalent and Non-Inhibitive Fluorimetric Markers for DPP III Enzyme

“…The synthetic route for compounds 1 and 2 is depicted in Scheme 2 . First, triarylborane alkyne A and the azido derivative of lysine amino acid B were prepared according to the literature [ 8 , 27 ]. Cu(I)-catalyzed 1,3-dipolar cycloaddition of A with B in anhydrous DMF and DIPEA at room temperature afforded conjugate C in good yield.…”

“…The synthetic route for compounds 1 and 2 is depicted in Sch triarylborane alkyne A and the azido derivative of lysine amino acid B w according to the literature [8,27]. Cu(I)-catalyzed 1,3-dipolar cycloaddition anhydrous DMF and DIPEA at room temperature afforded conjugate C i Deprotection of the Boc protecting group of compound C was performed method in TFA/CH2Cl2, and triazole-linked triarylborane amino acid con isolated in quantitative yield as a yellow powder.…”

Bis(phenylethynyl)arene Linkers in Tetracationic Bis‐triarylborane Chromophores Control Fluorimetric and Raman Sensing of Various DNAs and RNAs

“…Detailed investigation of these bio‐macromolecules and understanding of the interactions that influence their communication on a molecular level is a broad and interdisciplinary research field. One well‐established way to approach the subject is to study the interactions and binding behaviours of small molecules with DNA and RNA [6–17] …”

“…One well-established way to approach the subjecti st os tudy the interactions andb inding behaviours of small molecules with DNA and RNA. [6][7][8][9][10][11][12][13][14][15][16][17] There are three main binding modes, namely intercalation, groove binding and external binding (Figure 1). [22,23] For intercalation to occur,t he helical structureo ft he bio-macromole-cule needs to unwind to allow for as mall molecule to insert in between the coplanarly arranged nucleobases.…”

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

“…Since till now various NDI derivatives were applied for binding and sensing different types of DNA/RNA constructs, including G-quartets [ 55 – 57 ], and other, more complex sequences, the herein presented amino acid–NDI conjugates may in future also be investigated for such applications, either directly or incorporated in peptidoid constructs. Indeed, the colourful and fluorescent NDIs 3a and 3b are ideal for use in peptide-backbone constructed multichromophores targeting FRET-based sensing [ 14 , 26 , 58 ]. For the application of here presented results in bioanalytical sciences or biologically relevant studies it will be necessary to further modify the presented compounds and precisely collect information about their sensitivity to particular target, read-out accuracy, limits of detection, and selectivity at biorelevant conditions.…”