Tight Binding of a Dimeric Derivative of Vancomycin with Dimeric l -Lys- d -Ala- d -Ala

The ligand/receptor pair consisting of a synthetic dimeric derivative of vancomycin ( V ), linked at the C terminus by p -xylylenediamine ( V -CONHCH 2 C 6 H 4 CH 2 NHCO- V ), and a dimeric derivative of l -Lys- d -Ala- d -Ala, [CH 2 CON ε H(N α -Ac)- l -Lys- d -Ala- d -Ala-CO 2 - ] 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 (∼10 3 ) relative to the corresponding monomeric interaction between unmodified monomeric vancomycin and diacetyl- l -Lys- d -Ala- d -Ala.