Tight Binding of a Dimeric Derivative of Vancomycin with Dimeric <scp>l</scp>-Lys-<scp>d</scp>-Ala-<scp>d</scp>-Ala

The ligand/receptor pair consisting of a synthetic dimeric derivative of vancomycin (V), linked at the C terminus by p-xylylenediamine (V-CONHCH2C6H4CH2NHCO-V), and a dimeric derivative of l-Lys-d-Ala-d-Ala, [CH2CONεH(Nα-Ac)-l-Lys-d-Ala-d-Ala-CO2-]2, provides a new system with which to study the influence of divalency on the strength of binding. A competitive assay using affinity capillary electrophoresis (ACE) has been developed and used to estimate the dissociation constant of the divalent complex (≈ 1.1 nM) and the enhancement in binding (∼103) relative to the corresponding monomeric interaction between unmodified monomeric vancomycin and diacetyl-l-Lys-d-Ala-d-Ala.