Solution structure of a designed spirocyclic helical ligand binding at a two-base bulge site in DNA.

ABSTRACT: The solution structure of the complex formed between an oligodeoxynucleotide containing a two-base bulge (5'-CCATCGTCTACCTTTGGTAGGATGG) and SCA-alpha2, a designed spirocyclic helical molecule, has been elucidated. SCA-alpha2, a close mimic of the metabolite, NCSi-gb, of the DNA bulge-specific enediyne antibiotic neocarzinostatin, differs in possessing a more stable spirocyclic ring system and in lacking certain bulky groupings that compromise bulged DNA binding. This study provides a detailed comparison of the binding modes of the two complexes and provides new insights into the importance of shape and space, as opposed to simple nucleotide sequence, in complex formation at the bulge site. The two rigidly held aromatic rings of SCA-alpha2 form a right-handed helical molecular wedge that sp

SUBMITTER: Zhang N 

PROVIDER: S-EPMC2569200 | biostudies-literature | 2007 Apr

REPOSITORIES: biostudies-literature