Deciphering the pH-dependence of ground- and excited-state equilibria of thienoguanine

Abstract

Proposed photophysics of thGb under acidic conditions.

Real-Time Monitoring of Human Guanine Deaminase Activity by an Emissive Guanine Analog

“…p K a values were extrapolated by plotting the change in optical density versus pH (Figure d, Figure S2). The guanine derivatives, th G N and tz G N , show two p K a values (p K a = 4.41, 10.19 and p K a = 3.28, 8.96, respectively), while the xanthine derivatives, th X N and tz X N , show one p K a value (p K a = 9.92 and p K a = 8.8, respectively), as expected. ,, …”

“…The guanine derivatives, th G N and tz G N , show two pK a values (pK a = 4.41, 10.19 and pK a = 3.28, 8.96, respectively), while the xanthine derivatives, th X N and tz X N , show one pK a value (pK a = 9.92 and pK a = 8.8, respectively), as expected. 31,38,39 To compare the susceptibility of th G N and tz G N to GDAmediated deamination, enzymatic reactions were first analyzed by HPLC and then monitored in real-time by absorption and emission spectroscopy. HPLC analysis confirmed the complete transformation of native guanine to xanthine by GDA within 500 s (Figure 4a and S3a).…”

What Makes Thienoguanosine an Outstanding Fluorescent DNA Probe?

“…Importantly, th G exhibits rich information content, as it can exist in two tautomeric forms (i.e., H1 and H3 keto-amino tautomers) at neutral pH, exhibiting considerably shifted absorption and emission spectra and different fluorescent lifetimes. , The equilibrium between these tautomers informs on the local environment of th G. Due to its unique properties, th G was successfully used to monitor the local conformational changes associated with the binding of the HIV-1 nucleocapsid protein NCp7 to the (−)­Primer Binding Site (PBS) and to decipher the mechanism of the NCp7-promoted (+)/(−)­PBS annealing reaction . The fluorescent nucleoside analogue in its deoxyribo or in its ribo form has also been successfully used to monitor B to Z transitions of DNA, single nucleotide polymorphism, distance measurements in DNA, , base flipping reactions, ribozyme-mediated cleavage, and cellular activity of siRNAs …”

Harnessing an emissive guanine surrogate to design small-molecule fluorescent chemosensors of O6-methylguanine-DNA-methyltransferase (MGMT)

“…c Fluorescence quantum yield, reference: quinine sulphate in 0.5 M H 2 SO 4 (Φ = 0.546). d This value is higher than the one reported in the literature (0.48), 28 presumably due to the use of another quantum yield standard.…”

“…23,24 Among these, thienoguanosine ( th G), developed by Y. Tor et al, 25 represents an easily accessible, highly emissive surrogate of guanosine that almost perfectly mimics the latter in nucleic acids, making it an outstanding fluorescent DNA probe. 26,27 In this work, we harnessed fluorescence properties of the corresponding nucleobase surrogate, thienoguanine ( th G N , Scheme 1), 28 to design the smallest fluorescent chemosensors of MGMT activity.…”