A TRIVALENT SYSTEM FROM VANCOMYCIN-CENTER-DOT-D-ALA-D-ALA WITH HIGHERAFFINITY THAN AVIDIN-CENTER-DOT-BIOTIN

Tris(vancomycin carboxamide) binds a trivalent ligand derived from D-A la-D-Ala with very high affinity: dissociation constant (K-d) approxim ate to 4 x 10(-17) +/- 1 x 10(-17) M. High-affinity trivalent binding and monovalent binding are fundamentally different. In trivalent (and more generally, polyvalent) binding, dissociation occurs in stages, an d its rate can be accelerated by monovalent ligand at sufficiently hig h concentrations. In monovalent binding, dissociation is determined so lely by the rate constant for dissociation and cannot be accelerated b y added monomer. Calorimetric measurements for the trivalent system in dicate an approximately additive gain in enthalpy relative to the corr esponding monomers. This system is one of the most stable organic rece ptor-ligand pairs involving small molecules that is known. It illustra tes the practicality of designing very high-affinity systems based on polyvalency.