Polyoxazoline‐Peptide adducts that retain antibody avidity

Abstract

Synthetic polymers have long been used to modify various properties of proteins such as activity and solubility. Polyethylene glycol (PEG) has been widely used to form adducts with enzymes and antibodies. In this study, the polyoxazoline family of water-soluble polymers was used to synthesize adducts containing a synthetic peptide recognized by a monoclonal antibody (MAb) directed against human protein C (hPC). This is the first application of direct conjugation of unterminated or "living" polymer to a peptide. The avidity of the antibody for the various adducts was characterized with respect to size and hydrophilicity of methyl- and ethyl-substituted polyoxazoline polymers (POX). Avidity of the adducts was not found to be dependent upon the hydrophilicity and was slightly decreased due to polymer modification. The methyl-POX-peptide adducts were found to be highly water soluble, while the ethyl-POX-peptide adducts showed sporadic problems with aqueous solubility. Because the polymer-peptide adducts retained avidity for the antibody, polyoxazoline polymers may have potential application to protein-adduct chemistry.

Double-Hydrophilic Block Copolymers: Synthesis and Application as Novel Surfactants and Crystal Growth Modifiers

“…Hydrophilic, salt responsive block GTP [54] Poly(N-isopropylacrylamide), (PNIPAAm) [46,71,[73][74][75][76][77][78][79][80][81][82][83][84][85][86][87][88][89][90] patent by BASF where living PMMA anions were used to initiate the polymerization of ethylene oxide (EO). [21] The same strategy was reported in the literature.…”

“…[46] Living polyoxazoline was dried and redissolved in methanol before the solution was added in 20% aliquots of the theoretical 1 : 1 product to the methanol solution of the activated peptide. Although the overall yield was low (30%) and the reaction product was contaminated with free polyoxazoline homopolymer, the coupled peptide was found to have retained its activity towards a specific antibody.…”

Click‐Chemistry: An Alternative Way to Functionalize Poly(2‐methyl‐2‐oxazoline)

“…[5] Our interest has focused on poly(2-methyl-2-oxazoline) (POXZ), which is a hydrophilic and non-ionic polymer showing properties such as biocompatibility and lack of toxicity as evidenced by early studies in relation to the biomedical applications. [6][7][8] This polymer has a chemical structure similar to a pseudopolypeptide, which gives good resistance to degradation in the biological environment [9] .…”

The use of Fab‐masking antigens to enhance the activity of immobilized antibodies

“…We have previously characterized the avidity of the synthetic antigens used in these studies with HPC4-Mab. 22 In these previous studies, the peptide possessed an avidity for HPC4-Mab which was approximately twofold less than hPC. The 10K poly(2-methyloxazoline)-peptide adduct was shown to possess an avidity which was approximately 2-4-fold less than that of the peptide.…”