Rosa Zerella

Changes in motion vs. bonding in positively vs. negatively cooperative interactions

From a consideration of the interactions between non-covalent bonds, it is concluded that positively cooperative binding will occur with a benefit in enthalpy and a cost in entropy, and that negatively cooperative binding will occur with a cost in enthalpy and a benefit in entropy; experimental data support these conclusions.

Kinetic barriers and ordering of non-covalently bound states

Binding of a dimer of a glycopeptide antibiotic to two molecules of a ligand that are bound to a membrane surface (by a hydrocarbon anchor) has been investigated. This binding on a surface is cooperatively enhanced (surface enhancement) relative to the binding in solution, because the former occurs intramolecularly on a template. Previously a correlation between surface enhancement and thermodynamic stability of the dimer in free solution (Kdimsol) was hypothesised. However, we found that two weakly dimerising antibiotics (vancomycin and ristocetin A) with similar Kdimsol give very different surface enhancements. We propose a model to explain the data correlating surface enhancement to the kinetic barrier to dissociation of the dimer. The surface enhancement of binding can be expected to increase with increasing tightness of the non-covalent interactions formed at the dimer interface. The effect should be found in general where cooperativity is exercised within an organised template (e.g., DNA duplexes and proteins).

Aggregation, binding, and dimerisation studies of a teicoplanin aglycone analogue (LY154989)

LY154989 is a vancomycin group antibiotic closely related in structure to teicoplanin aglycone. In view of the clinical importance of teicoplanin, the dimerisation, aggregation, and binding of bacterial cell wall analogues by LY154989 are of interest. These properties have been studied by proton NMR spectroscopy. LY154989 has been shown to form concentration-dependent aggregates in aqueous solution, similar to those of teicoplanin, even though it does not possess a C11 acyl chain, which was hitherto thought to be the cause of this aggregation. The aggregation can be disrupted by the addition of bacterial cell wall precursor analogues such as Ac2-KDADA, Ac-DADA or Ac-DA. Thus, growing bacteria may disrupt aggregates of teicoplanin and LY154989. LY154989 dimerises weakly in aqueous solution and the dimerisation is weakly cooperative with ligand binding.