The thermodynamics and kinetics of binding of model tripeptides epsilon-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 glycidic side arms and modified at the terminal amino acids of the peptide backbone have been studied by fluorescence or UV spectroscopy. The binding process is suggested to occur via a two-step mechanism. The first, fast process is likely governed by an electrostatic interaction between the C- and N-termini of the peptide chain of the substrate and of the antibiotic, respectively, while the second slower one, accounts for the formation of the hydrogen bonds responsible of the major contribution to the overall binding energy. The binding constants with all modified derivatives are smaller than that with native teicoplanin Larger 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.
