Active-Site Targeting Paramagnetic Probe for Matrix Metalloproteinases

The design and synthesis of the Ln³⁺ complexes of a DOTA-containing (DOTA=1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) inhibitor of matrix metalloproteinases are reported. The tight binding of the sulfonamide scaffold to the catalytic domain of the investigated matrix metalloproteinase is not impaired by the presence of the Ln³⁺ -DOTA moiety. The paramagnetic properties of the Ln³⁺ complex are exploited to obtain insights into the structural features of the ligand-protein interactions and to evaluate the influence of the linker length on the quality of the paramagnetic restraints.