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Solution structure of a thrombin binding aptamer complex with a non-planar platinum(ii) compound

Thrombin Binding Aptamer (TBA) is a monomolecular well-defined two G-tetrad antiparallel G-quadruplex DNA that inhibits the activity of human α-thrombin. In this report, we synthesized a quasi-cross-shaped platinum(ii) compound (L′(2)LPt) with one cyclometalated and two carbene ligands. We found L′(...

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Autores principales: Zhu, Bo-Chen, He, Juan, Xia, Xiao-Yu, Jiang, Jingxing, Liu, Wenting, Liu, Liu-Yi, Liang, Bing-Bing, Yao, Hua-Gang, Ke, Zhuofeng, Xia, Wei, Mao, Zong-Wan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society of Chemistry 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9297526/
https://www.ncbi.nlm.nih.gov/pubmed/35919711
http://dx.doi.org/10.1039/d2sc01196d
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author Zhu, Bo-Chen
He, Juan
Xia, Xiao-Yu
Jiang, Jingxing
Liu, Wenting
Liu, Liu-Yi
Liang, Bing-Bing
Yao, Hua-Gang
Ke, Zhuofeng
Xia, Wei
Mao, Zong-Wan
author_facet Zhu, Bo-Chen
He, Juan
Xia, Xiao-Yu
Jiang, Jingxing
Liu, Wenting
Liu, Liu-Yi
Liang, Bing-Bing
Yao, Hua-Gang
Ke, Zhuofeng
Xia, Wei
Mao, Zong-Wan
author_sort Zhu, Bo-Chen
collection PubMed
description Thrombin Binding Aptamer (TBA) is a monomolecular well-defined two G-tetrad antiparallel G-quadruplex DNA that inhibits the activity of human α-thrombin. In this report, we synthesized a quasi-cross-shaped platinum(ii) compound (L′(2)LPt) with one cyclometalated and two carbene ligands. We found L′(2)LPt has selective affinity to bind the TBA G-quadruplex. A fibrinogen clotting assay revealed that L′(2)LPt can abrogate the inhibitory activity of TBA against thrombin. We solved the 1 : 1 L′(2)LPt–TBA complex structure by NMR, which revealed a unique self-adaptive property of L′(2)LPt upon binding to TBA. In the complex, a carbene ligand of L′(2)LPt rotates to pair with the cyclometalated ligand to form a plane stacking over half of the TBA G-tetrad and covered by lateral TT loops. It is notable that the heavy atom Pt stays out of the G-tetrad. Meanwhile, the other carbene ligand remains relatively perpendicular and forms a hydrogen bond with a guanine to anchor the L′(2)LPt position. This structure exhibits a quasi-cross-shaped Pt(ii) compound bound to the G-quadruplex with an unusual “wall-mounted” binding mode. Our structures provide insights into the specific recognition of antiparallel G-quadruplex DNA by a self-adaptive Pt(ii) compound and useful information for the design of selective G-quadruplex targeting non-planar molecules.
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spelling pubmed-92975262022-08-01 Solution structure of a thrombin binding aptamer complex with a non-planar platinum(ii) compound Zhu, Bo-Chen He, Juan Xia, Xiao-Yu Jiang, Jingxing Liu, Wenting Liu, Liu-Yi Liang, Bing-Bing Yao, Hua-Gang Ke, Zhuofeng Xia, Wei Mao, Zong-Wan Chem Sci Chemistry Thrombin Binding Aptamer (TBA) is a monomolecular well-defined two G-tetrad antiparallel G-quadruplex DNA that inhibits the activity of human α-thrombin. In this report, we synthesized a quasi-cross-shaped platinum(ii) compound (L′(2)LPt) with one cyclometalated and two carbene ligands. We found L′(2)LPt has selective affinity to bind the TBA G-quadruplex. A fibrinogen clotting assay revealed that L′(2)LPt can abrogate the inhibitory activity of TBA against thrombin. We solved the 1 : 1 L′(2)LPt–TBA complex structure by NMR, which revealed a unique self-adaptive property of L′(2)LPt upon binding to TBA. In the complex, a carbene ligand of L′(2)LPt rotates to pair with the cyclometalated ligand to form a plane stacking over half of the TBA G-tetrad and covered by lateral TT loops. It is notable that the heavy atom Pt stays out of the G-tetrad. Meanwhile, the other carbene ligand remains relatively perpendicular and forms a hydrogen bond with a guanine to anchor the L′(2)LPt position. This structure exhibits a quasi-cross-shaped Pt(ii) compound bound to the G-quadruplex with an unusual “wall-mounted” binding mode. Our structures provide insights into the specific recognition of antiparallel G-quadruplex DNA by a self-adaptive Pt(ii) compound and useful information for the design of selective G-quadruplex targeting non-planar molecules. The Royal Society of Chemistry 2022-06-23 /pmc/articles/PMC9297526/ /pubmed/35919711 http://dx.doi.org/10.1039/d2sc01196d Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by-nc/3.0/
spellingShingle Chemistry
Zhu, Bo-Chen
He, Juan
Xia, Xiao-Yu
Jiang, Jingxing
Liu, Wenting
Liu, Liu-Yi
Liang, Bing-Bing
Yao, Hua-Gang
Ke, Zhuofeng
Xia, Wei
Mao, Zong-Wan
Solution structure of a thrombin binding aptamer complex with a non-planar platinum(ii) compound
title Solution structure of a thrombin binding aptamer complex with a non-planar platinum(ii) compound
title_full Solution structure of a thrombin binding aptamer complex with a non-planar platinum(ii) compound
title_fullStr Solution structure of a thrombin binding aptamer complex with a non-planar platinum(ii) compound
title_full_unstemmed Solution structure of a thrombin binding aptamer complex with a non-planar platinum(ii) compound
title_short Solution structure of a thrombin binding aptamer complex with a non-planar platinum(ii) compound
title_sort solution structure of a thrombin binding aptamer complex with a non-planar platinum(ii) compound
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9297526/
https://www.ncbi.nlm.nih.gov/pubmed/35919711
http://dx.doi.org/10.1039/d2sc01196d
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