Two 1 : 1 binding modes for distamycin in the minor groove of d(GGCCAATTGG)

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Abstract
Single‐crystal X‐ray structure determinations of the complex between the minor‐groove binder distamycin and d(GGCCAATTGG) reveal two 1 : 1 binding modes which differ in the orientation of the drug molecule in the minor groove. The two crystals were grown from different crystallization conditions and found to diffract to 2.38 and 1.85 Å, respectively. The structures were refined to completion using SHELXL‐93, resulting in a residual R factor of 20.30% for the 2.38‐Å resolution structure (including 46 water molecules) and 19.74% for the 1.85‐Å resolution structure (including 74 water molecules). In both orientations, bifurcated hydrogen bonds are formed between the amide nitrogen atoms of the drug and AT base pairs. With a binding site of at least five base pairs, close contacts between the terminal distamycin atoms and guanine amino groups are inevitable. The detailed nature of several of these interactions was further investigated by ab initio quantum chemical methods.