FUNCTIONALIZED POLYMERS FOR SITE-SPECIFIC ATTACHMENT

摘要

Provided are organic polymers, e.g. poly(ethylene glycol), functionalized with an amino-oxy oxime-forming group and methods for their preparation and use in site-specific, chemoselective ligation to an aldehyde(or ketone)-functionalized target macromolecule or surface under mild ligation conditions. Multi-polymer-containing amino-oxy-functionalized or aldehyde(or ketone)-functionalized polymer constructs are also provided that allow site-specific, chemoselective ligation under mild conditions of the construct (and thus all of its polymers) to a single site on a target macromolecule via an oxime bond. Families of functionalized polymer constructs are also provided wherein each construct differs in topology but not in molecular weight (average) from the others in the same family. Methods for their use include the systematic modification of a target macromolecule to rapidly create a family of target molecules, preferably biologically important proteins, differing in topology but not molecular weight, from which family can be identified macromolecules having desired biological or physical properties, such as enhanced pharmacokinetic behavior.