An efficient and convenient approach for preparing a giant polypeptidepoly(ethylene oxide) triblock copolymer architecture of defined structure and composition is reported. This copolymer consists of two long polypeptide chains derived from bovine serum albumin of distinct lengths with stabilizing poly(ethylene oxide) side-chains, a connecting poly(ethylene oxide) block, and the presence of secondary structure elements along the polypeptide backbone. It is synthesized from the abundant plasma protein serum albumin and the polypeptide backbone is fully biodegradable. This approach represents a convenient and efficient strategy for preparing giant polypeptide-based block copolymers of defined structure via a semi-synthetic strategy. Such high-molecular-weight, biodegradable copolymers are attractive for various biomedical applications