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-CO NHCH2C6H4CH2NHCO-V), and a dimeric derivative of L-Lys-D-Ala-D-Ala, -H -epsilon(N-alpha-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 bin ding. A competitive assay using affinity capillary electrophoresis (AC E) has been developed and used to estimate the dissociation constant o f the divalent complex (K-d(d) approximate to 1.1 nM) and the enhancem ent in binding (similar to 10(3)) relative to the corresponding monome ric interaction between unmodified monomeric vancomycin and diacetyl-L -lys-D-Ala-D-Ala.