Fluorescent cyanine-guanidiniocarbonyl-pyrrole conjugate with pH-dependent DNA/RNA recognition and DPP III fluorescent labelling and inhibition properties

Abstract

Here designed and prepared cyanine-guanidinocarbonyl-pyrrole conjugate (Cy-GCP), intrinsically non-fluorescent, revealed fluorescent switch-on recognition of various secondary structures of ds-DNA and ds-RNA. Moreover, at the same submicromolar concentrations, DNA/RNA recognition was observed by selective induced (I)CD pattern in the visible range. Preliminary results showed that Cy-GCP strongly interacted with DPP III enzyme, switching-on the fluorescence upon binding and inhibiting enzyme action with efficiency comparable to the best-known inhibitor tynorphin.

Correction

“…showing somewhat better performances of these compounds than of the previously reported cyanine analogue inhibition efficiency (K i ¼ 370 nM) ( Smidlehner et al, 2018).…”

Fluorimetric and CD Recognition between Various ds-DNA/RNA Depends on a Cyanine Connectivity in Cyanine-guanidiniocarbonyl-pyrrole Conjugate

“…At variance to all previously studied aryl-GCP conjugates [ 10 , 11 , 12 , 13 , 14 , 15 ] and even the Cy-GCP [ 17 ] (very close analog of 2 ), no ICD bands of GCP chromophore (at λ = 300 nm) were observed, pointing out that for both, 1 and 2 , GCP moiety was not uniformly oriented in respect to the polynucleotide chiral axis [ 32 ], similar as previously noted for nucleobase-GCP analogs [ 33 ].…”

“…Previously studied Cy-GCP revealed aggregation properties in UV/Vis spectrum [ 17 ] comparable to its close analog 2 , pointing out that quinoline-tethered cyanines conjugated with GCP moiety are more prone to aggregation in comparison to benzothiazole-analogs ( 1 ).…”

“…We recently showed that isosteric cyanine conjugates with pyrene show some different properties in interaction with DNA/RNA and also proteins (BSA) as a result of different connectivity of the linker to the cyanine chromophore [ 16 ]. Very recently, we also prepared the first cyanine-GCP conjugate, which revealed promising selective fluorimetric and circular dichroism sensing between various ds-DNA or ds-RNA polynucleotides, which was additionally controllable by pH due to GCP [ 17 ]. Led by the aforementioned promising results, we designed and prepared novel analogs of cyanine-GCP conjugates, conjugates 1 and 2 , characterization of which we presented in this work.…”

“…In the design of new conjugates ( Scheme 1 ), we introduced an elongated linker with one more CH 2 − group, with respect to the afore-studied analog [ 17 ] to increase flexibility, and we changed cyanine substituent “Cl” with “Br”. A larger volume of “Br” is likely to block intercalation of cyanine moiety between DNA/RNA base pairs, thus directing small molecule to the DNA or RNA grooves, which could result in the high sensitivity to binding site properties (namely, grooves of various ds-DNA or ds-RNA differ considerably—see Table S1, Supplementary Materials ).…”