2MB3

Solution structure of an intramolecular (3+1) human telomeric G-quadruplex bound to a telomestatin derivative

Summary for 2MB3

• Entry DOI: 10.2210/pdb2mb3/pdb
• NMR Information: BMRB: 19387
• Descriptor: DNA_(5'-D(*TP*TP*GP*GP*GP*TP*TP*AP*GP*GP*GP*TP*TP*AP*GP*GP*GP*TP*TP*AP*GP*GP*GP*A)-3'), (12S,27S)-12,27-bis(4-aminobutyl)-4,30-dimethyl-3,7,14,18,22,29-hexaoxa-11,26,31,32,33,34,35,36-octaazaheptacyclo[26.2. 1.1~2,5~.1~6,9~.1~13,16~.1~17,20~.1~21,24~]hexatriaconta-1(30),2(36),4,6(35),8,13(34),15,17(33),19,21(32),23,28(31)-dode caene-10,25-dione (2 entities in total)
• Functional Keywords: intramolecular g-quadruplex, human telomere, anticancer targets, macrocyclic hexaoxazole, telomestatin derivative, dna-dna inhibitor complex, dna/dna inhibitor
• Total number of polymer chains: 1
• Total formula weight: 8278.56

Authors

Chung, W.J.,Heddi, B.,Tera, M.,Iida, K.,Nagasawa, K.,Phan, A.T. (deposition date: 2013-07-24, release date: 2013-08-28, Last modification date: 2024-05-15)

Primary citation

Chung, W.J.,Heddi, B.,Tera, M.,Iida, K.,Nagasawa, K.,Phan, A.T.
Solution structure of an intramolecular (3 + 1) human telomeric g-quadruplex bound to a telomestatin derivative.
J.Am.Chem.Soc., 135:13495-13501, 2013

PubMed Abstract: Guanine-rich human telomeric DNA can adopt secondary structures known as G-quadruplexes, which can be targeted by small molecules to achieve anticancer effects. So far, the structural information on complexes between human telomeric DNA and ligands is limited to the parallel G-quadruplex conformation, despite the high structural polymorphism of human telomeric G-quadruplexes. No structure has been yet resolved for the complex with telomestatin, one of the most promising G-quadruplex-targeting anticancer drug candidates. Here we present the first high-resolution structure of the complex between an intramolecular (3 + 1) human telomeric G-quadruplex and a telomestatin derivative, the macrocyclic hexaoxazole L2H2-6M(2)OTD. This compound is observed to interact with the G-quadruplex through π-stacking and electrostatic interactions. This structural information provides a platform for the design of topology-specific G-quadruplex-targeting compounds and is valuable for the development of new potent anticancer drugs.

PubMed: 23909929
DOI: 10.1021/ja405843r

Experimental method

SOLUTION NMR