Exceptionally Selective and Tunable Sensing of Guanine Derivatives and Analogues by Structural Complementation in a G‐Quadruplex

Abstract

Aguanine-vacancy-bearing G-quadruplex (GVBQ) interacts with guanine and derivatives by as tructural complementation to form am ore stable and intact G-quadruplex. Sensors using GVBQs are devised to detect guanine and other nucleobases,a nd their derivatives derived from structurally similar compounds.Astrict requirement of Hoogsteen hydrogen bonds between the GVBQ and analyte in the structural complementation confers exceptional selectivity on the analyte. As such,s ubtle modifications on analytes affecting even as ingle hydrogen bond can preclude the recognition. In principle,t he strategy may also be expanded to detect many planar cyclic compounds.B ecause nucleobases and derivatives/metabolites are involved in many physiological and pathological processes,t his type of sensor mayf ind applications in risk assessment of pathogenesis and therapeutics related to nucleic acid metabolism.

Engineering base-excised aptamers for highly specific recognition of adenosine

“…1B). 35,36 Although rebinding of the deleted parts has been demonstrated in both methods, the specicity remained poor. For example, the abasic-site-contained DNA duplex can bind both adenosine and theophylline based on cytosine recognition, 32,40 and the vacancybearing G-quadruplex can accept guanosine, GMP, GDP and GTP with similar affinities.…”

“…For example, the abasic-site-contained DNA duplex can bind both adenosine and theophylline based on cytosine recognition, 32,40 and the vacancybearing G-quadruplex can accept guanosine, GMP, GDP and GTP with similar affinities. 36 In our work here, a new method of DNA engineering is described in Fig. 1C, in which a whole nucleotide is excised, and a break is created (a new 3 0 end and a new 5 0 end).…”

“…This was achieved either by introducing an abasic-site in the duplex, [32][33][34] or by omitting a whole guanine-nucleotide in a G-quadruplex. [35][36][37] These DNA complexes can reach a mM K d , and behave like traditional aptamers. However, they oen have a low specicity.…”

“…However, they oen have a low specicity. Not only the cognate analytes can t into the vacancy, 36 pseudo-base pairing may also induce binding. 32,38 This may be attributed to their recognition largely relying on secondary structural discrimination (simple base pairing).…”

Escherichia coli DNA polymerase I can disrupt G‐quadruplex structures during DNA replication

“…Considering that a guanine vacancy in one of the G-quartet layers (GVBQ) can be filled by a guanine base from GTP or GMP to complete an intact Gquartet [47,48], the number of potential G4s was increased from 52 to 356 (Table 2), corresponding to a G4 occurrence frequency of 1.96&, higher than that of canonical 3-G4 DNAs. The above analysis and prediction indicate that G4 DNAs exist in the E. coli genome and may be roadblocks for Pols in genome transaction processes.…”