Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.653818
Title: Structure determination of contrast agents for angiogenesis imaging by high resolution nuclear magnetic resonance spectroscopy
Author: Lenoir, Marc
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2006
Availability of Full Text:
Access from EThOS:
Full text unavailable from EThOS. Please try the link below.
Access from Institution:
Abstract:
Structure of bicyclic pseudo octapeptides containing a sequence arginine-glycine-aspartic acid (RGD peptides) was investigated by high-resolution NMR spectroscopy. The compounds, synthesized by General Electric Healthcare, are used as contract agents in imaging of cancer. Structures were generated using different protocols in vacuum or explicit solvent. The best results were obtained through the analysis of a series of NOESY spectra acquired using varying mixing times. Full relaxation matrix analysis in explicit solvent was performed on these data yielding a consistent set of structure. The polyethylene glycol moiety and the metal binding site did not show any signs of tertiary structure. The distance restraints for structure calculations were supplemented by dihedral restraints provided by the analysis of vicinal coupling constants. Towards this end, an extensive set of coupling constants related to dihedral angles of amino acids was obtained. Various experiments, including HMBC, HSQC and HETLOC, were evaluated yielding a basic set of experiments suitable for the measurement of coupling constants of peptides with natural abundance of isotopes. The structures of the studied peptides were found to be similar and to adopting a reverse γ-turn centered on the aspartic acid of the RGD motif. Despite the bicycling nature of these peptides the compounds showed signs of flexibility, which was more pronounced in H2O. Side chains of the compounds are flexible as implied from the analysis of the distributions of cl angles. Structures were determined in two solvents, H2O and DMSO. It was found that the water based structures are more extended, while the DMSO based structure are more compact. DMSO structure of one peptide was compared with a published NMR structure of a similar peptide and a good agreement was found for the common RGD loop. The water based structures are similar to a published X-ray structure of a RGD peptide in complex with αvβ3.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.653818  DOI: Not available
Share: