1I5V

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

Summary for 1I5V

• Entry DOI: 10.2210/pdb1i5v/pdb
• Descriptor: 5'-D(*CP*GP*AP*TP*CP*G)-3', 2-(PYRIDO[1,2-E]PURIN-4-YL)AMINO-ETHANOL (2 entities in total)
• Functional Keywords: drug-dna complex, double helix, dna
• Total number of polymer chains: 2
• Total formula weight: 4076.91

Authors

Favier, A.,Blackledge, M.,Simorre, J.P.,Marion, D.,Debousy, J.C. (deposition date: 2001-03-01, release date: 2001-03-14, Last modification date: 2024-05-22)

Primary citation

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

Experimental method

SOLUTION NMR