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.