Book of Abstracts: Albany 2007

category image Albany 2007
Conversation 15
June 19-23 2007

(3+1) G-quadruplex Structures of the Human Telomere in K+ Solution

Intramolecular G-quadruplexes formed by the human telomeric G-rich strand are promising anticancer targets. We present two different intramolecular G-quadruplex structures formed by human telomeric sequences in K+ solution (1, 2). Both structures (Form 1 and Form 2) contain the (3+1) G-tetrad core, in which three G-tracts are oriented in one direction and the fourth in the opposite direction, with one double-chain-reversal and two edgewise loops. However, Form 2 (2) differs from Form 1 (1) by loop arrangements: the double-chain-reversal loop is formed by the third linker in Form 2 instead of the first linker in Form 1. This result indicates the robustness of the (3+1) G-quadruplex scaffold, whose topological characteristics should provide a unique platform for structure-based anticancer drug design targeted to human telomeric DNA. Our data also support the view that multiple human telomeric G-quadruplex conformations coexist in K+ solution. Furthermore, even small changes to flanking sequences can perturb the equilibrium between different coexisting G-quadruplex forms.

References and Footnotes
  1. Luu K. N., Phan A. T., Kuryavyi V., Lacroix L., Patel D. J. J. Am. Chem. Soc. 128, 9963-9970 (2006).
  2. Phan A. T., Luu K. N., Patel D. J. Nucleic Acids Res. 34, 5715-5719 (2006).

A. T. Phan1,2,*
K. N. Luu1
V. Kuryavyi1
L. Lacroix3
D. J. Patel1

1Structural Biology Program
Memorial Sloan-Kettering Cancer Center
New York, USA
2School of Physical & Mathematical Sciences
Nanyang Technological University, Singapore
3Museum National d?Histoire Naturelle
Paris, France