Duplex Healing of Selectively Thiolated Guanosine Mismatches through a Cd(2+) Chemical Stimulus



Lunn SML, Hribesh S, Whitfield CJ, Hall MJ, Houlton A, Bronowska AK, Tuite EM, Pike AR.


Chembiochem. 2018 Mar 25. doi: 10.1002/cbic.201800100. Online ahead of print.


The on-column selective conversion of guanosine to thioguanosine (tG) yields modified oligomers that exhibit destabilisation over the fully complementary duplex. Restoration to a stabilised duplex is induced through thio-directed Cd(2+) coordination; a route for healing DNA damage. Short oligomers are G-specifically thiolated through a modified on-column protocol without the need for costly thioguanosine phosphoramidites. Addition of Cd(2+) ions to a duplex containing a highly disrupted tG central mismatch sequence, 3′-A(6) tG(4) T(6) -5′, suggests a (tG)(8) Cd(2) central coordination regime, resulting in increased base stacking and duplex stability. Equilibrium molecular dynamic calculations support the hypothesis of metal-induced healing of the thiolated duplex. The 2 nm displacement of the central tG mismatched region is dramatically reduced after the addition of a chemical stimuli, Cd(2+) ions, returning to a minimized fluctuational state comparable to the unmodified fully complementary oligomer. CI – © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

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Link/DOI: 10.1002/cbic.201800100