Probing the interaction of distamycin A with S100β: the “unexpected” ability of S100β to bind to DNA‐binding ligands

DNA-minor-groove-binding ligands are potent antineoplastic molecules. The antibiotic distamycin A is the prototype of one class of these DNA-interfering molecules that have been largely used in vitro. The affinity of distamycin A for DNA is well known, and the structural details of the complexes with some B-DNA and G-quadruplex-forming DNA sequences have been already elucidated. Here, we show that distamycin A binds S100β, a protein involved in the regulation of several cellular processes. The reported affinity of distamycin A for the calcium(II)-loaded S100β reinforces the idea that some biological activities of the DNA-minor-groove-binding ligands arise from the binding to cellular proteins.