1VZK

A Thiophene Based Diamidine Forms a "Super" AT Binding Minor Groove Agent

Summary for 1VZK

• Entry DOI: 10.2210/pdb1vzk/pdb
• Related: 2DBE
• Descriptor: 5'-D(*CP*GP*CP*GP*AP*AP*TP*TP*CP*GP *CP*G)-3', 2-(5-{4-[AMINO(IMINO)METHYL]PHENYL}-2-THIENYL)-1H-BENZIMIDAZOLE-6- CARBOXIMIDAMIDE DIHYDROCHLORIDE, MAGNESIUM ION, ... (4 entities in total)
• Functional Keywords: nucleic acid, nucleic acids, minor groove binder, double helix, dna-drug complex, magnesium-water complex, dna hydration
• Total number of polymer chains: 2
• Total formula weight: 7711.52

Authors

Mallena, S.,Lee, M.P.H.,Bailly, C.,Neidle, S.,Kumar, A.,Boykin, D.W.,Wilson, W.D. (deposition date: 2004-05-20, release date: 2004-10-25, Last modification date: 2023-12-13)

Primary citation

Mallena, S.,Lee, M.P.H.,Bailly, C.,Neidle, S.,Kumar, A.,Boykin, D.W.,Wilson, W.D.
Thiophene-Based Diamidine Forms a "Super" at Binding Minor Groove Agent
J.Am.Chem.Soc., 142:13659-, 2004

PubMed 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.

PubMed: 15493923
DOI: 10.1021/JA048175M

Experimental method

X-RAY DIFFRACTION (1.77 Å)