Poly-L-hydroxyproline(PHyp)represents an important model for comprehending the polyproline II helix and holds immense potential for broad biomedical applications.The synthesis of PHyp,however,involves inefficient prot...Poly-L-hydroxyproline(PHyp)represents an important model for comprehending the polyproline II helix and holds immense potential for broad biomedical applications.The synthesis of PHyp,however,involves inefficient protection-deprotection steps and has been restricted to low molecular weight(MW)and linear topology.Here,we report the first ring-opening polymerization(ROP)of unprotected hydroxyproline N-carboxyanhydride(Hyp-NCA)for the facile synthesis of PHyp with tunable linear or branching topologies.While linear PHyp was readily prepared with control via water-assisted polymerization in minutes,tertiary amine-mediated ROP of Hyp-NCA affords branched PHyp(B-PHyp)for the first time with MW up to 438 kDa,∼40 times higher than the previous record.Experimental and computational studies collectively uncovered fresh insights into the general mechanism regarding the hydroxy/amine selectivity.Postpolymerization modification of B-PHyp affords injectable hydrogels with a critical gelization concentration as low as 1.0%.This study provides an approach that may inspire the development of novel synthetic collagen-like biomaterials.展开更多
基金supported by the National Natural Science Foundation of China(grant nos.22331002 and 22125101)the Beijing Natural Science Foundation Key Project(grant no.Z220023)+1 种基金the Peking University Clinical Medicine plus X(grant no.ZX002)the Open Funding Project of the State Key Laboratory of Biochemical Engineering and Key Laboratory of Biopharmaceutical Preparation and Delivery(grant no.2023KF-01).
文摘Poly-L-hydroxyproline(PHyp)represents an important model for comprehending the polyproline II helix and holds immense potential for broad biomedical applications.The synthesis of PHyp,however,involves inefficient protection-deprotection steps and has been restricted to low molecular weight(MW)and linear topology.Here,we report the first ring-opening polymerization(ROP)of unprotected hydroxyproline N-carboxyanhydride(Hyp-NCA)for the facile synthesis of PHyp with tunable linear or branching topologies.While linear PHyp was readily prepared with control via water-assisted polymerization in minutes,tertiary amine-mediated ROP of Hyp-NCA affords branched PHyp(B-PHyp)for the first time with MW up to 438 kDa,∼40 times higher than the previous record.Experimental and computational studies collectively uncovered fresh insights into the general mechanism regarding the hydroxy/amine selectivity.Postpolymerization modification of B-PHyp affords injectable hydrogels with a critical gelization concentration as low as 1.0%.This study provides an approach that may inspire the development of novel synthetic collagen-like biomaterials.
