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
In our previous studies, DAZAP2 gene expression was down-regulated inuntreated patients of multiple myeloma (MM). For better studying the structure and function ofDAZAP2, a full-length cDNA was isolated from mononucle...In our previous studies, DAZAP2 gene expression was down-regulated inuntreated patients of multiple myeloma (MM). For better studying the structure and function ofDAZAP2, a full-length cDNA was isolated from mononuclear cells of a normal human bone marrow,sequenced and deposited to Genbank (AY430097). This sequence has an identical ORF (open readingframe) as the NM.014764 from human testis and the D31767 from human cell line KG-1. Phylogeneticanalysis and structure prediction reveal that DAZAP2 homologues are highly conserved throughoutevolution and share a polyproline region and several potential SH2/SH3 binding sites. DAZAP2 occursas a single-copy gene with a four-exon organization. We further noticed that the functional DAZAP2gene is located on Chromosome 12 and its pseudogene gene is on Chromosome 2 with electronic locationof human chromosome in Genbank, though no genetic abnormalities of MM have been reported onChromosome 12. The ORF of human DAZAP2 encodes a 17-kDa protein, which is highly similar to mousePrtb. The DAZAP2 protein is mainly localized in cytoplasm with a discrete pattern of punctuateddistribution. DAZAP2 may associate with carcinogenesis of MM and participate in yet-to-be identifiedsignaling pathways to regulate proliferation and differentiation of plasma cells.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.
基金grants (No.39880021,30270750, 30300406) from the National Natural Science Foundation of China. The accession numbers of the nucleotide sequences deposited to the GenBank are AY430097, AY490096, AY490097, and AY490098.
文摘In our previous studies, DAZAP2 gene expression was down-regulated inuntreated patients of multiple myeloma (MM). For better studying the structure and function ofDAZAP2, a full-length cDNA was isolated from mononuclear cells of a normal human bone marrow,sequenced and deposited to Genbank (AY430097). This sequence has an identical ORF (open readingframe) as the NM.014764 from human testis and the D31767 from human cell line KG-1. Phylogeneticanalysis and structure prediction reveal that DAZAP2 homologues are highly conserved throughoutevolution and share a polyproline region and several potential SH2/SH3 binding sites. DAZAP2 occursas a single-copy gene with a four-exon organization. We further noticed that the functional DAZAP2gene is located on Chromosome 12 and its pseudogene gene is on Chromosome 2 with electronic locationof human chromosome in Genbank, though no genetic abnormalities of MM have been reported onChromosome 12. The ORF of human DAZAP2 encodes a 17-kDa protein, which is highly similar to mousePrtb. The DAZAP2 protein is mainly localized in cytoplasm with a discrete pattern of punctuateddistribution. DAZAP2 may associate with carcinogenesis of MM and participate in yet-to-be identifiedsignaling pathways to regulate proliferation and differentiation of plasma cells.
