Characterisation of domain fragments of recombinant human albumin
Characterisation of domain fragments of recombinant human albumin
Recombinant domain fragments of human serum albumin consisting of domains 1 and 2 (D21) and domains 2 and 3 (D23) have been produced. Both fragments have been shown to retain secondary structural characteristics similar to that of the full length protein. The binding of site-specific ligands dansylglycine and dansylsarcosine to D21 and D23 has been characterised and compared to that with recombinant human albumin and human serum albumin from human plasma. These studies showed that both fragments possess functional ligand binding sites, but with binding characteristics different from those of the full-length protein. The stereoselectivity of the fragments. and full-length proteins towards the enantiomers of warfarin and ibuprofen was also examined. All the proteins exhibited a higher affinity for the R-enantiomer of warfarin, with HSA, rHA and D23 showing a two-fold greater affinity for the R-enantiomer over the S-enantiomer. The D21 fragment, however, showed almost a four-fold greater affinity for the R-enantiomer of warfarin.
The albumin molecule is known to undergo a conformational change, known as the neutral to base transition, over the pH range 6.0 - 9.0. The effect of this transition upon the binding of warfarin and its enantiomers to albumin and the domain fragments was investigated. The binding of ibuprofen and its enantiomers to human serum albumin., recombinant human albumin and the domain fragments was investigated. No stereoselectivity towards the enantiomers was observed.
University of Southampton
1999
Twine, Susan Melanie
(1999)
Characterisation of domain fragments of recombinant human albumin.
University of Southampton, Doctoral Thesis.
Record type:
Thesis
(Doctoral)
Abstract
Recombinant domain fragments of human serum albumin consisting of domains 1 and 2 (D21) and domains 2 and 3 (D23) have been produced. Both fragments have been shown to retain secondary structural characteristics similar to that of the full length protein. The binding of site-specific ligands dansylglycine and dansylsarcosine to D21 and D23 has been characterised and compared to that with recombinant human albumin and human serum albumin from human plasma. These studies showed that both fragments possess functional ligand binding sites, but with binding characteristics different from those of the full-length protein. The stereoselectivity of the fragments. and full-length proteins towards the enantiomers of warfarin and ibuprofen was also examined. All the proteins exhibited a higher affinity for the R-enantiomer of warfarin, with HSA, rHA and D23 showing a two-fold greater affinity for the R-enantiomer over the S-enantiomer. The D21 fragment, however, showed almost a four-fold greater affinity for the R-enantiomer of warfarin.
The albumin molecule is known to undergo a conformational change, known as the neutral to base transition, over the pH range 6.0 - 9.0. The effect of this transition upon the binding of warfarin and its enantiomers to albumin and the domain fragments was investigated. The binding of ibuprofen and its enantiomers to human serum albumin., recombinant human albumin and the domain fragments was investigated. No stereoselectivity towards the enantiomers was observed.
This record has no associated files available for download.
More information
Published date: 1999
Identifiers
Local EPrints ID: 464055
URI: http://eprints.soton.ac.uk/id/eprint/464055
PURE UUID: f23a03ad-f46f-4296-8ba3-ae18634082fd
Catalogue record
Date deposited: 04 Jul 2022 21:01
Last modified: 04 Jul 2022 21:01
Export record
Contributors
Author:
Susan Melanie Twine
Download statistics
Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.
View more statistics