Synthetic polypeptides are one of the most important biocompatible and biodegradable polymers, which have well-defined secondary structures and have been widely studied for biomedical applications, such as tissue engineering, drug and gene delivery, bioadhesive, antimicrobial, biosensors and diagnostics. To take the applications a step further, many bioactive polypeptides were designed and prepared. Bioactive polypeptides are usually synthesized by introducing of bioactive agents into the polypeptide backbones, including peptides, proteins, biotins, targeting ligands, polysaccharides, monosaccharides, antigens/antibodies and electroactive groups, etc.. However, limitations still remain in the preparation of the polypeptides since the lack of reactive groups in the polypeptide backbone. To improve the synthesis of bioactive polypeptides for further medical applications, two versatile approaches were developed by our group recently. The first one is to conjugate thermo-responsive polymers (e.g. poly(N-isopropyl acryamide)) or reactive agents (e.g. cinnamyl group) with pH-responsive polypeptides (e.g. poly(L-glutamic acid) and poly(L-lysine)). The tunable stimuli-responsive behaviors combined with the good biodegradability may endow these materials with great potential for biomedical applications. The other one is to introduce reactive groups such as alkyne, chloride, azide and allyl into the synthetic polypeptides as side groups through the ring-opening polymerization of functional monomers, which can be developed through postpolymerization modifications to prepare bioactive polypeptides. Sugars and stimuli-responsive oligomers or polymers have been successful conjugated into the polypeptides and their properties were studied.
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