Abstract
A study of calicheamicin γ1I complexed to seven different recognition sites is presented. The recognition sites encompass a range of oligopyrimidine sites that present different topological features in the minor groove. Intermolecular NOE networks for the different calicheamicin-DNA complexes show that the drug binds in the same mode to each recognition site. Calicheamicin binding also induces a set of characteristic conformational changes in the DNA in each complex that maximize the complementarity of the fit between calicheamicin and the DNA. Based on an analysis of the different complexes as well as biochemical information on cleavage preferences, we propose that calicheamicin displays a shape-selective preference for pyrimidine tracts through an induced-fit mechanism. We predict that any carbohydrate that maintains the overall shape of the calicheamicin oligosaccharide will exhibit similar sequence selectivity. This hypothesis is supported by experiments on calicheamicin oligosaccharide analogues repo...
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