Poly y-D-glutamic acid as a template for functionalised water-soluble biomaterials
Poly y-D-glutamic acid as a template for functionalised water-soluble biomaterials
Polymeric materials can provide a very useful template for the delivery of biologically active small molecules, provided that the polymer can be efficiently functionalised, giving a high local concentration of attached ligands.
Bacillus licheniformis is encapsulated by a homopolymer of D-glutamic acid residues. It consists of a linear sequence of D-glutamic acid units linked via their γ-carboxylates, giving an unusual γ-linked polypeptide of high molecular weight (150-200kDa).
Poly γ-D-glutamic acid offers several advantages for such studies, it is a high molecular weight, water-soluble polymer that is bio-compatible, its α-carboxylate sidechains can be covalently modified in aqueous solution, its γ-linked D-amino acid backbone is resistant to mammalian proteases.
The immobilisation of protein ligands on the polymer can lead to several applications including the immobilisation of tumour-specific antibodies which bind to multimeric receptors on tumour cell surface (with Dr M. Glennie, Tenovus Research Dept.. SGH). Synthetics linkers bearing an iodoacetyl or a maleimide functional group were developed and attached to the polymer via a free amino group. Lysosyme and antibody (anti CD40) were then attached to the conjugate via a reaction with a free thiol from a cysteinyl residue. The immobilisation of glycopeptides (vancomycin) and glycosides onto the Poly γ-D-glutamic acid was also investigated and the biological activity of the conjugates tested.
University of Southampton
Prodhomme, Emmanuel J.P.F
cfed1f12-0add-414e-8e93-f9c2646856ff
2001
Prodhomme, Emmanuel J.P.F
cfed1f12-0add-414e-8e93-f9c2646856ff
Prodhomme, Emmanuel J.P.F
(2001)
Poly y-D-glutamic acid as a template for functionalised water-soluble biomaterials.
University of Southampton, Doctoral Thesis.
Record type:
Thesis
(Doctoral)
Abstract
Polymeric materials can provide a very useful template for the delivery of biologically active small molecules, provided that the polymer can be efficiently functionalised, giving a high local concentration of attached ligands.
Bacillus licheniformis is encapsulated by a homopolymer of D-glutamic acid residues. It consists of a linear sequence of D-glutamic acid units linked via their γ-carboxylates, giving an unusual γ-linked polypeptide of high molecular weight (150-200kDa).
Poly γ-D-glutamic acid offers several advantages for such studies, it is a high molecular weight, water-soluble polymer that is bio-compatible, its α-carboxylate sidechains can be covalently modified in aqueous solution, its γ-linked D-amino acid backbone is resistant to mammalian proteases.
The immobilisation of protein ligands on the polymer can lead to several applications including the immobilisation of tumour-specific antibodies which bind to multimeric receptors on tumour cell surface (with Dr M. Glennie, Tenovus Research Dept.. SGH). Synthetics linkers bearing an iodoacetyl or a maleimide functional group were developed and attached to the polymer via a free amino group. Lysosyme and antibody (anti CD40) were then attached to the conjugate via a reaction with a free thiol from a cysteinyl residue. The immobilisation of glycopeptides (vancomycin) and glycosides onto the Poly γ-D-glutamic acid was also investigated and the biological activity of the conjugates tested.
Text
842404.pdf
- Version of Record
More information
Published date: 2001
Identifiers
Local EPrints ID: 464663
URI: http://eprints.soton.ac.uk/id/eprint/464663
PURE UUID: 9b2d9f42-8283-494a-9d02-297489b15124
Catalogue record
Date deposited: 04 Jul 2022 23:55
Last modified: 16 Mar 2024 19:41
Export record
Contributors
Author:
Emmanuel J.P.F Prodhomme
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