Polysaccharide−polypeptide conjugates have gained a broad interest in mimicking the structure and bioactivity of peptidoglycans or proteoglycans for biomedical applications. Efficient and precise preparation of the conjugates is challenging and unresolved, mainly because of the mismatched solubility between polysaccharide initiators and N-carboxyanhydrides (NCAs), which frequently results in competing side reactions and oligomeric polypeptide chain. Herein, we report a facile and efficient strategy to prepare the conjugates with well-controlled polypeptide chain length (l p ) directly from unmodified polysaccharides via a biphasic solution ring-opening polymerization. The effect of l p on surface antibacterial properties has been investigated. Elongating the l p can significantly potentiate the antibiofilm property of the conjugate coatings. Our results may provide opportunities to develop various polypeptide-based conjugates with well-defined structures toward versatile uses.

Inspired by the charge composition and distribution of proteins and peptides, we designed and prepared a series of brush polypeptides with positive and negative charges separately distributed in the side chains and the backbones. The brush polypeptides can self-or co-deposit on various substrates forming ultrathin and stable coatings. They showed potent bactericidal activity and antibiofilm property, outperforming conventional linear polypeptide coatings with randomly distributed positive and negative charges. Keeping the balance of positive/negative charges and increasing the numbers of positive/negative charges can further improve the antibacterial property of brush polypeptide coatings without sacrificing their biocompatibility.

Comprehensive SummaryWhile the accelerated polymerization of N‐carboxyanhydrides (NCAs) has been utilized to synthesize versatile polypeptide materials in an efficient manner with minimized side reactions, the preparation of polypeptide‐based inorganic/organic hybrid materials with the acceleration strategy remained largely unexplored. Herein, we report the accelerated ring‐opening polymerization (ROP) of NCAs mediated by amine‐modified inorganic nano‐initiators, such as mesoporous silica nanoparticles (MSN‐NH2), which is driven by the cooperative effect of the neighboring α‐helical polypeptide chains in a dichloromethane (DCM)/water biphasic system. Well‐defined nano‐hybrids were prepared within 15 min from non‐purified NCA monomers, through in situ purification and subsequent ultrafast polymerization process. NCAs can be rapidly initiated by amino groups of MSN uniformly dispersed at the interface of DCM and water, and subsequently formed the well‐defined polypeptides within 15 min. The prepared inorganic/organic nano‐hybrid with MSN as the core and polypeptide as the shell adopted spherical morphology and uniform size distribution due to the excellent controllability of ROP. Besides, this system is also suitable for a variety of NCAs and inorganic nano‐initiators. This research allows efficient and rapid preparation of inorganic/organic nano‐hybrids, and further promotes the extensive application of this material in the biomedical fields.