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Duplex Healing of Selectively Thiolated Guanosine Mismatches through a Cd 2+ Chemical Stimulus
Author(s) -
Lunn Samantha M. L.,
Hribesh Samira,
Whitfield Colette J.,
Hall Michael J.,
Houlton Andrew,
Bronowska Agnieszka K.,
Tuite Eimer M.,
Pike Andrew R.
Publication year - 2018
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201800100
Subject(s) - duplex (building) , destabilisation , guanosine , chemistry , oligomer , chemical stability , stereochemistry , biophysics , dna , organic chemistry , biochemistry , psychology , social psychology , biology
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.