Final Report Summary - WBAWBA (Polymer conjugation of peptides/salmon calcitonin for increased efficacy)
The objectives of this project were the development of a new peptide conjugation strategy which has the potential to overcome the limitations of the commercially successful, conventional pegylation with linear polymers. In addition, we explored the application of Single electron transfer living radical polymerisation (SET-LRP) for this purpose. The major part of this research was focused on the synthesis and characterisation of a-functional comb polymers by living radical polymerisation techniques. Moreover, sugar carrying polymers were synthesised and their lectin binding properties were investigated.
A new online polymerisation monitoring technique using FT-IR probe has been developed to assess the single electron transfer living radical polymerisation in DMSO. This allowed us to monitor the polymerisation parameters in an accelerated manner. In parallel, we have utilised a rapid GPC technique to follow Cu(0) mediated polymerisation by means of molecular weight and molecular weight distribution.
Conjugation of a polymer chain and a peptide or protein is not straightforward process and needs to be optimised for each type of polymer and peptide. Therefore, we have investigated base catalysed thiol-ene click reactions to improve this process. Various thiol compounds were reacted with poly(ethylene glycol) methacrylate monomers in the presence of amine and phosphine catalysts. The optimum catalysts, reaction time and other various conditions could be determined by this systematic structure-property relationship study. Moreover, we have extended this study for conjugation of comb-shaped poly(ethyleneglycol) methacrylate polymers with vinyl terminus to different thiol compounds.
Carbohydrates have great importance in biochemical reactions. Therefore, the synthesis and characterisation of carbohydrate containing polymers (glycopolymers) have been investigated. We have summarised the state-of-the-art on synthesis of glycopolymers using click reactions in a recent review article. Furthermore, we have introduced a one-pot synthesis technique of carbohydrates with azide functionality. Finally, we have tested a small library of glycopolymers for their specific lectin recognition properties. These polymers showed superb properties and significantly inhibit the binding of dendritic cell lectins (DC-SIGN) to human immunoefficiency virus isolated glycoprotein (gp120).
Following to this project, we will investigate for alternative synthesis techniques of glycopolymers in various architectures and sugars and improve the binding to specific lectins. These polymers will bring a unique biorecognition property to the polymer-peptide bioconjugates.
A new online polymerisation monitoring technique using FT-IR probe has been developed to assess the single electron transfer living radical polymerisation in DMSO. This allowed us to monitor the polymerisation parameters in an accelerated manner. In parallel, we have utilised a rapid GPC technique to follow Cu(0) mediated polymerisation by means of molecular weight and molecular weight distribution.
Conjugation of a polymer chain and a peptide or protein is not straightforward process and needs to be optimised for each type of polymer and peptide. Therefore, we have investigated base catalysed thiol-ene click reactions to improve this process. Various thiol compounds were reacted with poly(ethylene glycol) methacrylate monomers in the presence of amine and phosphine catalysts. The optimum catalysts, reaction time and other various conditions could be determined by this systematic structure-property relationship study. Moreover, we have extended this study for conjugation of comb-shaped poly(ethyleneglycol) methacrylate polymers with vinyl terminus to different thiol compounds.
Carbohydrates have great importance in biochemical reactions. Therefore, the synthesis and characterisation of carbohydrate containing polymers (glycopolymers) have been investigated. We have summarised the state-of-the-art on synthesis of glycopolymers using click reactions in a recent review article. Furthermore, we have introduced a one-pot synthesis technique of carbohydrates with azide functionality. Finally, we have tested a small library of glycopolymers for their specific lectin recognition properties. These polymers showed superb properties and significantly inhibit the binding of dendritic cell lectins (DC-SIGN) to human immunoefficiency virus isolated glycoprotein (gp120).
Following to this project, we will investigate for alternative synthesis techniques of glycopolymers in various architectures and sugars and improve the binding to specific lectins. These polymers will bring a unique biorecognition property to the polymer-peptide bioconjugates.