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Mirror‐Image Dependence: Targeting Enantiomeric G‐Quadruplex DNA Using Triplex Metallohelices
Author(s) -
Zhao Chuanqi,
Song Hualong,
Scott Peter,
Zhao Andong,
TateishiKarimata Hisae,
Sugimoto Naoki,
Ren Jinsong,
Qu Xiaogang
Publication year - 2018
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201809207
Subject(s) - dna , enantiomer , chemistry , stereochemistry , g quadruplex , entropy (arrow of time) , dna sequencing , biophysics , crystallography , biochemistry , biology , physics , quantum mechanics
Natural d ‐DNA and l ‐DNA are mirror‐image counterparts. However, because of the inherent flexibility and conformation diversity of DNA, it is still not clear how enantiomeric compounds recognize d ‐DNA and l ‐DNA. Herein, taking G‐quadruplex (G4) DNA as an example that has diverse conformations and distinct biofunctions, the binding of ten pairs of iron triplex metallohelices to d ‐ and l ‐G4 DNA were evaluated. The Δ‐enantiomer binds to d ‐DNA and the Λ‐enantiomer binds to l ‐DNA, exhibiting almost the same stabilization effect and binding affinity. The binding affinity of the Δ‐metallohelix with d ‐G4 is nearly 70‐fold higher than that of Λ‐metallohelix binding d ‐G4. Δ‐Metallohelix binding to d ‐G4 follows a two‐step binding process driven by a favorable enthalpy contribution to compensate for the associated unfavorable entropy.