PDBsum entry 1vzk

Nucleic acid

PDB id: 1vzk

Contents

DNA/RNA

Ligands

D1B

Metals

_MG

Waters ×60

PDB id:

1vzk

Name:

Nucleic acid

Title:

A thiophene based diamidine forms a "super" at binding minor groove agent

Structure:

5'-d( Cp Gp Cp Gp Ap Ap Tp Tp Cp Gp Cp G)-3'. Chain: a, b. Engineered: yes

Source:

Synthetic: yes

Biol. unit:

Dimer (from PDB file)

Resolution:

1.77Å R-factor: 0.223 R-free: 0.295

Authors:

S.Mallena,M.P.H.Lee,C.Bailly,S.Neidle,A.Kumar,D.W.Boykin,W.D.Wilson

Key ref:

S.Mallena et al. (2004). Thiophene-based diamidine forms a "super" at binding minor groove agent. J Am Chem Soc, 126, 13659-13669. PubMed id: 15493923 DOI: 10.1021/ja048175m

Date:

20-May-04 Release date: 25-Oct-04

DNA/RNA chains

C-G-C-G-A-A-T-T-C-G-C-G 12 bases

C-G-C-G-A-A-T-T-C-G-C-G 12 bases

DOI no: 10.1021/ja048175m

J Am Chem Soc 126:13659-13669 (2004)

PubMed id: 15493923

Thiophene-based diamidine forms a "super" at binding minor groove agent.

S.Mallena, M.P.Lee, C.Bailly, S.Neidle, A.Kumar, D.W.Boykin, W.D.Wilson.

ABSTRACT

The DNA minor groove is the interaction site for many enzymes and transcription control proteins and as a result, development of compounds that target the minor groove is an active research area. In an effort to develop biologically active minor groove agents, we are preparing and exploring the DNA interactions of a systematic set of diamidine derivatives with a powerful array of methods including DNase I footprinting, biosensor-SPR methods, and X-ray crystallography. Surprisingly, conversion of the parent phenyl-furan-phenyl diamidine to a phenyl-thiophene-benzimidazole derivative yields a compound with over 10-fold-increased affinity for the minor groove at AT sequences. Single conversion of the furan to a thiophene or a phenyl to benzimidazole does not cause a similar increase in affinity. X-ray results indicate a small bond angle difference between the C-S-C angle of thiophene and the C-O-C angle of furan that, when amplified out to the terminal amidines of the benzimidazole compounds, yields a very significant difference in the positions of the amidines and their DNA interaction strength.