KINETICS AND THERMODYNAMICS OF BINDING OF A MODEL TRIPEPTIDE TO TEICOPLANIN AND ANALOGOUS SEMISYNTHETIC ANTIBIOTICS

The thermodynamics and kinetics of binding of model tripeptides epsilo n-N-acetyl-alpha-N-dansyI-L-Lys-D-Ala-D-Ala (ADLAA) or alpha-N,epsilon -N-diacetyl-L-Lys-D-Ala-D-Ala (AALAA) to teicoplanin (la) and a series of semisynthetic derivatives with (1b-f) or devoid of (2a-g) the glyc idic side arms and modified at the terminal amino acids of the peptide backbone have been studied by fluorescence or UV spectroscopy. The bi nding process is suggested to occur via a two-step mechanism. The firs t, fast process is likely governed by an electrostatic interaction bet ween the C- and N-termini of the peptide chain of the substrate and of the antibiotic, respectively, while the second slower one, accounts f or the formation of the hydrogen bonds responsible of the major contri bution to the overall binding energy. The binding constants with all m odified derivatives are smaller than that with native teicoplanin Larg er modification of the overall binding constant are observed when the sugar residues are removed and, to a lower extent, when the N-terminus of the peptide chain is acylated. The kinetic process is very little affected by the modifications introduced.