ANALYTICAL PARTITIONING OF POLY(ETHYLENE GLYCOL)-MODIFIED PROTEINS

Covalently grafting proteins with varying numbers (n) of poly(ethylene glycol) molecules (PEGs) often enhances their biomedical and industri al usefulness. Partition between the phases in aqueous polymer two-pha se systems can be used to rapidly characterize polymer-protein conjuga tes in a manner related to various enhancements. The logarithm of the partition coefficient (K) approximates linearity over the range O<n<x. However, x varies with the nature of the conjugate (e.g., protein mol ecular mass) and such data analysis does not facilitate the comparison of varied conjugates. The known behavior of surface localized PEGs su ggests a better correlation should exist between log K and the weight fraction of polymer in PEG-protein conjugates. Data from four independ ent studies involving three proteins (granulocyte-macrophage colony st imulation factor, bovine serum albumin and immunoglobulin G) has been found to support this hypothesis. Although somewhat simplistic, 'weigh t fraction' based analysis of partition data appears robust enough to accommodate laboratory to laboratory variation in protein, polymer and phase system type. It also facilitates comparisons between partition data involving disparate polymer-protein conjugates.