P. Scrimin et al., KINETICS AND THERMODYNAMICS OF BINDING OF A MODEL TRIPEPTIDE TO TEICOPLANIN AND ANALOGOUS SEMISYNTHETIC ANTIBIOTICS, Journal of organic chemistry, 61(18), 1996, pp. 6268-6272
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.