Solution Structure of a G-quadruplex Bound to the Bisquinolinium Compound Phen-DC3†
Wan Jun Chung
School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore 637371 (Singapore)
These authors contributed equally.
Search for more papers by this authorDr. Brahim Heddi
School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore 637371 (Singapore)
These authors contributed equally.
Search for more papers by this authorDr. Florian Hamon
Institut Curie, Section Recherche, CNRS, UMR 176, Université Paris-Sud, Bat. 110–112, 91405 Orsay (France)
Search for more papers by this authorCorresponding Author
Dr. Marie-Paule Teulade-Fichou
Institut Curie, Section Recherche, CNRS, UMR 176, Université Paris-Sud, Bat. 110–112, 91405 Orsay (France)
Marie-Paule Teulade-Fichou, Institut Curie, Section Recherche, CNRS, UMR 176, Université Paris-Sud, Bat. 110–112, 91405 Orsay (France)
Anh Tuân Phan, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore 637371 (Singapore)
Search for more papers by this authorCorresponding Author
Prof. Dr. Anh Tuân Phan
School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore 637371 (Singapore)
Marie-Paule Teulade-Fichou, Institut Curie, Section Recherche, CNRS, UMR 176, Université Paris-Sud, Bat. 110–112, 91405 Orsay (France)
Anh Tuân Phan, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore 637371 (Singapore)
Search for more papers by this authorWan Jun Chung
School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore 637371 (Singapore)
These authors contributed equally.
Search for more papers by this authorDr. Brahim Heddi
School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore 637371 (Singapore)
These authors contributed equally.
Search for more papers by this authorDr. Florian Hamon
Institut Curie, Section Recherche, CNRS, UMR 176, Université Paris-Sud, Bat. 110–112, 91405 Orsay (France)
Search for more papers by this authorCorresponding Author
Dr. Marie-Paule Teulade-Fichou
Institut Curie, Section Recherche, CNRS, UMR 176, Université Paris-Sud, Bat. 110–112, 91405 Orsay (France)
Marie-Paule Teulade-Fichou, Institut Curie, Section Recherche, CNRS, UMR 176, Université Paris-Sud, Bat. 110–112, 91405 Orsay (France)
Anh Tuân Phan, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore 637371 (Singapore)
Search for more papers by this authorCorresponding Author
Prof. Dr. Anh Tuân Phan
School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore 637371 (Singapore)
Marie-Paule Teulade-Fichou, Institut Curie, Section Recherche, CNRS, UMR 176, Université Paris-Sud, Bat. 110–112, 91405 Orsay (France)
Anh Tuân Phan, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore 637371 (Singapore)
Search for more papers by this authorThis research was supported by the Singapore Ministry of Education and Nanyang Technological University (grants to A.T.P.). Phen-DC3 is a phenanthroline dicarboxamide bisquinolinium.
Graphical Abstract
Evidence stacks up for π-stacking: The structure of the complex formed between Phen-DC3, which specifically targets G-quadruplexes and exhibits potent biological activity in vivo, and an intramolecular G-quadruplex derived from the c-myc promoter was solved by NMR spectroscopy. Phen-DC3 was found to interact with the quadruplex through extensive π-stacking with guanine bases of the top G-tetrad (see picture).
Abstract
Phen-DC3 is a highly promising compound that specifically targets G-quadruplexes, with potent biological effects observed in vivo. We used NMR spectroscopy to solve the structure of the complex formed between Phen-DC3 and an intramolecular G-quadruplex derived from the c-myc promoter. Structural information revealed that Phen-DC3 interacts with the quadruplex through extensive π-stacking with guanine bases of the top G-tetrad. On the basis of our structure, modifications are proposed for the development of this compound for selective targeting of a specific G-quadruplex conformation.
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