1I5V

SOLUTION STRUCTURE OF 2-(PYRIDO[1,2-E]PURIN-4-YL)AMINO-ETHANOL INTERCALATED IN THE DNA DUPLEX D(CGATCG)2

1I5V の概要

• エントリーDOI: 10.2210/pdb1i5v/pdb
• 分子名称: 5'-D(*CP*GP*AP*TP*CP*G)-3', 2-(PYRIDO[1,2-E]PURIN-4-YL)AMINO-ETHANOL (2 entities in total)
• 機能のキーワード: drug-dna complex, double helix, dna
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 4076.91

構造登録者

Favier, A.,Blackledge, M.,Simorre, J.P.,Marion, D.,Debousy, J.C. (登録日: 2001-03-01, 公開日: 2001-03-14, 最終更新日: 2024-05-22)

主引用文献

Favier, A.,Blackledge, M.,Simorre, J.P.,Crouzy, S.,Dabouis, V.,Gueiffier, A.,Marion, D.,Debouzy, J.C.
Solution structure of 2-(pyrido[1,2-e]purin-4-yl)amino-ethanol intercalated in the DNA duplex d(CGATCG)2.
Biochemistry, 40:8717-8726, 2001

PubMed Abstract: The solution structure of the complex formed between d(CGATCG)(2) and 2-(pyrido[1,2-e]purin-4-yl)amino-ethanol, a new antitumor drug under design, has been resolved using NMR spectroscopy and restrained molecular dynamic simulations. The drug molecule intercalates between each of the CpG dinucleotide steps with its side chain lying in the minor groove. Analysis of NMR data establishes a weak stacking interaction between the intercalated ligand and the DNA bases; however, the drug/DNA affinity is enhanced by a hydrogen bond between the hydroxyl group of the end of the intercalant side chain and the amide group of guanine G6. Unrestrained molecular dynamic simulations performed in a water box confirm the stability of the intercalation model. The structure of the intercalated complex enables insight into the structure-activity relationship, allowing rationalization of the design of new antineoplasic agents.

PubMed: 11467931
DOI: 10.1021/bi0024963

実験手法

SOLUTION NMR