1vzk
From Proteopedia
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A THIOPHENE BASED DIAMIDINE FORMS A "SUPER" AT BINDING MINOR GROOVE AGENT
Overview
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.
About this Structure
1VZK is a Single protein structure of sequence from [1] with MG and D1B as ligands. Structure known Active Site: AC1. Full crystallographic information is available from OCA.
Reference
Thiophene-based diamidine forms a "super" at binding minor groove agent., Mallena S, Lee MP, Bailly C, Neidle S, Kumar A, Boykin DW, Wilson WD, J Am Chem Soc. 2004 Oct 27;126(42):13659-69. PMID:15493923
Page seeded by OCA on Mon Nov 5 15:19:45 2007
