Recognition and stabilization of quadruplex DNA by a potent new telomerase inhibitor: NMR studies of the 2:1 complex of a pentacyclic methylacridinium cation with d(TTAGGGT)4

Evripidis Gavathiotis; Robert A. Heald; Malcolm F.G. Stevens; Mark S. Searle

doi:10.1002/1521-3773(20011217)40:24<4749::AID-ANIE4749>3.0.CO;2-I

Recognition and stabilization of quadruplex DNA by a potent new telomerase inhibitor: NMR studies of the 2:1 complex of a pentacyclic methylacridinium cation with d(TTAGGGT)₄

Evripidis Gavathiotis, Robert A. Heald, Malcolm F.G. Stevens, Mark S. Searle

Research output: Contribution to journal › Article › peer-review

81 Scopus citations

Abstract

Guided by 24 drug-DNA NOEs, the complex formed between RHPS4 (a novel fluorinated polycyclic methylacridinium salt with potent telomerase activity) and d(TTAGGGT)₄ has been modeled by using MD simulations with drug molecules intercalated at the ApG and GpT steps. A low-energy structure for the 2:1 complex has a partial positive charge on the acridine 13-N atom (which acts as a pseudo potassium ion) positioned above the center of the G-tetrad (see picture).

Original language	English (US)
Pages (from-to)	4749-4751
Number of pages	3
Journal	Angewandte Chemie - International Edition
Volume	40
Issue number	24
DOIs	https://doi.org/10.1002/1521-3773(20011217)40:24<4749::AID-ANIE4749>3.0.CO;2-I
State	Published - Dec 17 2001
Externally published	Yes

Keywords

DNA recognition
G-quadruplex
NMR spectroscopy
Telomerase

ASJC Scopus subject areas

Catalysis
General Chemistry

Access to Document

10.1002/1521-3773(20011217)40:24<4749::AID-ANIE4749>3.0.CO;2-I

Cite this

Gavathiotis, E., Heald, R. A., Stevens, M. F. G., & Searle, M. S. (2001). Recognition and stabilization of quadruplex DNA by a potent new telomerase inhibitor: NMR studies of the 2:1 complex of a pentacyclic methylacridinium cation with d(TTAGGGT)₄. Angewandte Chemie - International Edition, 40(24), 4749-4751. https://doi.org/10.1002/1521-3773(20011217)40:24<4749::AID-ANIE4749>3.0.CO;2-I

Recognition and stabilization of quadruplex DNA by a potent new telomerase inhibitor: NMR studies of the 2:1 complex of a pentacyclic methylacridinium cation with d(TTAGGGT)₄. / Gavathiotis, Evripidis; Heald, Robert A.; Stevens, Malcolm F.G. et al.
In: Angewandte Chemie - International Edition, Vol. 40, No. 24, 17.12.2001, p. 4749-4751.

Research output: Contribution to journal › Article › peer-review

Gavathiotis, E, Heald, RA, Stevens, MFG & Searle, MS 2001, 'Recognition and stabilization of quadruplex DNA by a potent new telomerase inhibitor: NMR studies of the 2:1 complex of a pentacyclic methylacridinium cation with d(TTAGGGT)₄', Angewandte Chemie - International Edition, vol. 40, no. 24, pp. 4749-4751. https://doi.org/10.1002/1521-3773(20011217)40:24<4749::AID-ANIE4749>3.0.CO;2-I

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abstract = "Guided by 24 drug-DNA NOEs, the complex formed between RHPS4 (a novel fluorinated polycyclic methylacridinium salt with potent telomerase activity) and d(TTAGGGT)4 has been modeled by using MD simulations with drug molecules intercalated at the ApG and GpT steps. A low-energy structure for the 2:1 complex has a partial positive charge on the acridine 13-N atom (which acts as a pseudo potassium ion) positioned above the center of the G-tetrad (see picture).",

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