Higher‐Order Human Telomeric G‐Quadruplex DNA Metalloenzymes Enhance Enantioselectivity in the Diels–Alder Reaction. Issue 4 (11th February 2015)

• Record Type: Journal Article
• Authors: Li, Yinghao; Jia, Guoqing; Wang, Changhao; Cheng, Mingpan; Li, Can
• Is Part Of: Chembiochem. Volume 16:Issue 4(2015)
• Page Start: 618
• Page End: 624
• Publication Date: 2015-02-11
• Subjects: Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1002/cbic.201402692
• Languages: English
• ISSNs: 1439-4227

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>Short human telomeric (HT) DNA sequences form single G‐quadruplex (G₄) units and exhibit structure‐based stereocontrol for a series of reactions. However, for more biologically relevant higher‐order HT G₄‐DNAs (beyond a single G₄ unit), the catalytic performances are unknown. Here, we found that higher‐order HT G₄‐DNA copper metalloenzymes (two or three G₄ units) afford remarkably higher enantioselectivity (&gt;90 % <italic>ee</italic>) and a five‐ to sixfold rate increase, compared to a single G₄ unit, for the Diels–Alder reaction. Electron paramagnetic resonance (EPR) and enzymatic kinetic studies revealed that the distinct catalytic function between single and higher‐order G₄‐DNA copper metalloenzymes can be attributed to different Cu^II coordination environments and substrate specificity. Our finding suggests that, like protein enzymes and ribozymes, higher‐order structural organization is crucial for G₄‐DNA‐based catalysis.</p> </abstract>