2MCC

Structural studies on dinuclear ruthenium(II) complexes that bind diastereoselectively to an anti-parallel folded human telomere sequence

Summary for 2MCC

• Entry DOI: 10.2210/pdb2mcc/pdb
• Related: 2MCO
• NMR Information: BMRB: 19435
• Descriptor: human_telomere_quadruplex, tetrakis(2,2'-bipyridine-kappa~2~N~1~,N~1'~)(mu-tetrapyrido[3,2-a:2',3'-c:3'',2''-h:2''',3'''-j]phenazine-1kappa~2~N~4~,N~5~:2kappa~2~N~13~,N~14~)diruthenium(4+) (2 entities in total)
• Functional Keywords: dna, quadruplex, complex, ruthenium
• Total number of polymer chains: 1
• Total formula weight: 8194.76

Authors

Williamson, M.P.,Wilson, T.,Thomas, J.A.,Felix, V.,Costa, P.J. (deposition date: 2013-08-18, release date: 2013-10-02, Last modification date: 2024-05-15)

Primary citation

Wilson, T.,Costa, P.J.,Felix, V.,Williamson, M.P.,Thomas, J.A.
Structural Studies on Dinuclear Ruthenium(II) Complexes That Bind Diastereoselectively to an Antiparallel Folded Human Telomere Sequence.
J.Med.Chem., 56:8674-8683, 2013

PubMed Abstract: We report DNA binding studies of the dinuclear ruthenium ligand [{Ru(phen)2}2tpphz](4+) in enantiomerically pure forms. As expected from previous studies of related complexes, both isomers bind with similar affinity to B-DNA and have enhanced luminescence. However, when tested against the G-quadruplex from human telomeres (which we show to form an antiparallel basket structure with a diagonal loop across one end), the ΛΛ isomer binds approximately 40 times more tightly than the ΔΔ, with a stronger luminescence. NMR studies show that the complex binds at both ends of the quadruplex. Modeling studies, based on experimentally derived restraints obtained for the closely related [{Ru(bipy)2}2tpphz](4+), show that the ΛΛ isomer fits neatly under the diagonal loop, whereas the ΔΔ isomer is unable to bind here and binds at the lateral loop end. Molecular dynamics simulations show that the ΔΔ isomer is prevented from binding under the diagonal loop by the rigidity of the loop. We thus present a novel enantioselective binding substrate for antiparallel basket G-quadruplexes, with features that make it a useful tool for quadruplex studies.

PubMed: 24088028
DOI: 10.1021/jm401119b

Experimental method

SOLUTION NMR