Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.363149
Title: Energetics of interaction between biomolecules
Author: McPhail, Deborah
ISNI:       0000 0001 3389 1143
Awarding Body: University of Glasgow
Current Institution: University of Glasgow
Date of Award: 1997
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Abstract:
Thermodynamic aspects of the molecular recognition between the antibiotics vancomycin and ristocetin in the absence and presence of bacterial cell wall analogue peptides over a range of conditions has been investigated. Microcalorimetry has been used to study the recognition processes directly by measuring the association/dimerisation constants and enthalpy changes. Vancomycin has been shown to combine with various peptides, such as N-acetyl-D-Ala, N-acetyl-D-Ala-D-Ala, N-fumaryl-D-Ala and Nalpha,Nepsilon-diacetyl-Lys-D-Ala-D-Ala, but most strongly with Nalpha,Nepsilon-diacetyl-Lys-D-Ala-D-Ala, the amino acid sequence most closely resembling its natural substrate. Dimerisation of antibiotic in the presence of this ligand was significantly increased from dimerisation in the absence of ligand. This enhancement of vancomycin dimerisation in the presence of ligand is in contrast to ristocetin. kistocetin dimerisation in the absence ana presence of the cell wail analogues, N-acetyi-D-Ala and Nalpha,Nepsilon-diacetyl-Lys-D-Ala-D-Ala was similarly studied, but in this case, dimerisation was weakest in the presence of Nalpha,Nepsilon-diacetyl-Lys-D-Ala-D-Ala. Kinetics were used in an attempt to study the vancomycin dimerisation process in the presence of the strongly binding Nalpha,Nepsilon-diacetyl-Lys-D-Ala-D-Ala in more detail and a scheme is proposed for the direct dissociation of such dimers in solution. The precipitation of vancomycin/N-acetyl-D-Ala-D-Ala solutions at the concentrations required for calorimetric dilution measurements allowed successful crystallisation of the complex, which permitted the use of X-ray crystallography to investigate the structure of the complex. However, this remains unresolved due to an uncharacteristically large unit cell for a small molecule, the high symmetry space group and the lack of a suitable model for molecular replacement techniques.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.363149  DOI: Not available
Keywords: Antibiotics; Microcalorimetry
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