Calicheamicin-DNA recognition: An analysis of seven different drug-DNA complexes

A study of calicheamicin gamma(1)(I) complexed to seven different recogniti on sites is presented. The recognition sites encompass a range of oligopyri midine sites that present different topological features in the minor groov e, Intermolecular NOE networks for the different calicheamicin-DNA complexe s show that the drug binds in the sa,ne mode to each recognition site. Cali cheamicin binding also induces a set of characteristic conformational chang es 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 co mplexes as well as biochemical information on cleavage preferences. we prop ose 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 exper iments on calicheamicin oligosaccharide analogues reported in the following contribution.