Configurationally imprinted biomimetic polymers with specific recognition for oligopeptides

The over-expression of several peptides and proteins in the body often leads to catastrophic physiological conditions. Ultimately it would be beneficial to be able to reduce the circulation of these peptides. To achieve this, we created systems that use synthetic biomaterials to mimic natural biological recognition processes. These recognitive polymer systems can be fabricated with molecular architectures possessing specific chemical moieties that provide a framework for selective recognition of a target analyte in aqueous environments. We concentrate on a particular peptide, angiotensin II, which would benefit from a system such as this. This work reports on a novel recognitive system that recognizes and captures the undesirable analyte. To achieve destruction of the over-expressed peptide for further therapeutic effects, we have incorporated biodegradable components into the polymer backbone which create an acidic microenvironment, capable of destroying the peptide, upon hydrolytic cleavage at the ester bond. Imprinted polymer networks were prepared by UV-initiated, free radical polymerization reactions of acrylamide as the functional monomer, poly(ethylene glycol dimethacrylate) as the crosslinking agent, and angiotensin II as the template molecule. To analyze the effectiveness of the imprinting process, recognitive/binding studies using angiotensin II and its derivative SVA angiotensin were conducted by HPLC. In order to optimize the repeated recognition (rebinding) of angiotensin II, the molar ratio of template to functional monomer was varied from 1:8, 1:16 to 1:32. The cross-linking ratio was also varied from 10% to 80%. The angiotensin II was then placed in various acid compositions and analyzed by mass spectroscopy in order to determine its integrity in the presence of an acidic microenvironment. The recognition studies showed that the networks imprinted for angiotensin II were more selective and recognized angiotensin II more effectively than the non-imprinted polymers and was more selective for angiotensin II than its derivative peptide SVA angiotensin. It can also be seen from studies that the peptide angiotensin II can be degraded in the presence of glycolic acid. The synergistic effect of the recognition, capturing and destruction of the peptide ultimately offers promise for novel drug delivery systems.