PolyPEG-carboxyl is reactive with amine in the presence of activating agent, such as EDC or HATU. EDC reacts with carboxyl to yield an active O-acylisourea intermediate that is easily displaced by nucleophile from primary amine. The primary amine forms a stable amide bond with the original carboxyl group, and an EDC by-product is released as a soluble urea derivative.