Pasteurella multocida hyaluronan synthase (PmHAS) is a bi-functional glycosyltransferase, containing a β1,3-glucuronyltransferase and β1,4-N-acetylglucosaminetransferase domain. PmHAS catalyzes the elongation of hya...Pasteurella multocida hyaluronan synthase (PmHAS) is a bi-functional glycosyltransferase, containing a β1,3-glucuronyltransferase and β1,4-N-acetylglucosaminetransferase domain. PmHAS catalyzes the elongation of hyaluronan (HA) through the sequential addition of single monosaccharides to the non-reducing end of the hyaluronan chain. Research is focused on the relation between the length of the HA oligosaccharide and the single-step elongation kinetics from HA4 up to HA9. It was found that the turnover number kcat increased with length to maximum values of 11 and 14 s-1 for NAc- and UA-transfer, respectively. Interestingly, the specificity constant kcat/KM increased with polymer length from HA5 to HA7 to a value of 44 mM-1s-1, indicating an oligosaccharide binding site with increasing specificity towards a heptasaccharide at the UA domain. The value of kcat/KM remained moderately constant around 8 mM-1s-1 for HA4, HA6, and HA8, indicating a binding site with significantly lower binding specificity at the NAc domain than at the UA domain. These findings are further corroborated by a structural homology model of PmHAS, revealing two distinct sites for binding of oligosaccharides of different sizes, one in each transferase domain. Structural alignment studies between PmHAS and glycosyltransferases of the GT-A fold showed significant similarity in the binding of the UDP-sugars and the orientation of the acceptor substrate. These similarities in substrate orientation in the active site and in essential amino acid residues involved in substrate binding were utilized to localize the two HA oligosaccharide binding sites.展开更多
This feature article summarizes the synthesis of novel olefin block copolymers using fast syndiospecific living homo- and copolymerization of propylene, higher 1-alkene, and norbornene with ansa-fluorenylamidodimethyl...This feature article summarizes the synthesis of novel olefin block copolymers using fast syndiospecific living homo- and copolymerization of propylene, higher 1-alkene, and norbornene with ansa-fluorenylamidodimethyltitanium- based catalyst according to the authors＇ recent results. The catalytic synthesis of monodisperse polyolefin and olefin block copolymer was also described using this living system.展开更多
蛋白质-高分子偶联物是一类重要的长效化蛋白质,已被用于多种重大疾病的诊疗之中.探究新型、高效、温和的方法用以制备结构明确且功能可控的蛋白质-高分子偶联物是该领域所面对的重要科学问题.近年来,本课题组及同行将“蛋白质定点修饰...蛋白质-高分子偶联物是一类重要的长效化蛋白质,已被用于多种重大疾病的诊疗之中.探究新型、高效、温和的方法用以制备结构明确且功能可控的蛋白质-高分子偶联物是该领域所面对的重要科学问题.近年来,本课题组及同行将“蛋白质定点修饰”和“原位可控聚合”2种技术有机整合,提出了“蛋白质定点原位可控聚合”(site-specific in situ controlled polymerization,SICP)的方法,用以替代传统的聚乙二醇化技术,并在生物医学应用上取得了良好的进展.本专论主要从SICP方法的发展背景和内涵、蛋白质的定点修饰、原位可控聚合,以及SCIP在生物医学领域的应用等几个方面详细介绍SICP方法的研究进展,并对该方法未来的研发方向进行了简要的总结和展望.展开更多
文摘Pasteurella multocida hyaluronan synthase (PmHAS) is a bi-functional glycosyltransferase, containing a β1,3-glucuronyltransferase and β1,4-N-acetylglucosaminetransferase domain. PmHAS catalyzes the elongation of hyaluronan (HA) through the sequential addition of single monosaccharides to the non-reducing end of the hyaluronan chain. Research is focused on the relation between the length of the HA oligosaccharide and the single-step elongation kinetics from HA4 up to HA9. It was found that the turnover number kcat increased with length to maximum values of 11 and 14 s-1 for NAc- and UA-transfer, respectively. Interestingly, the specificity constant kcat/KM increased with polymer length from HA5 to HA7 to a value of 44 mM-1s-1, indicating an oligosaccharide binding site with increasing specificity towards a heptasaccharide at the UA domain. The value of kcat/KM remained moderately constant around 8 mM-1s-1 for HA4, HA6, and HA8, indicating a binding site with significantly lower binding specificity at the NAc domain than at the UA domain. These findings are further corroborated by a structural homology model of PmHAS, revealing two distinct sites for binding of oligosaccharides of different sizes, one in each transferase domain. Structural alignment studies between PmHAS and glycosyltransferases of the GT-A fold showed significant similarity in the binding of the UDP-sugars and the orientation of the acceptor substrate. These similarities in substrate orientation in the active site and in essential amino acid residues involved in substrate binding were utilized to localize the two HA oligosaccharide binding sites.
文摘This feature article summarizes the synthesis of novel olefin block copolymers using fast syndiospecific living homo- and copolymerization of propylene, higher 1-alkene, and norbornene with ansa-fluorenylamidodimethyltitanium- based catalyst according to the authors＇ recent results. The catalytic synthesis of monodisperse polyolefin and olefin block copolymer was also described using this living system.
文摘蛋白质-高分子偶联物是一类重要的长效化蛋白质,已被用于多种重大疾病的诊疗之中.探究新型、高效、温和的方法用以制备结构明确且功能可控的蛋白质-高分子偶联物是该领域所面对的重要科学问题.近年来,本课题组及同行将“蛋白质定点修饰”和“原位可控聚合”2种技术有机整合,提出了“蛋白质定点原位可控聚合”(site-specific in situ controlled polymerization,SICP)的方法,用以替代传统的聚乙二醇化技术,并在生物医学应用上取得了良好的进展.本专论主要从SICP方法的发展背景和内涵、蛋白质的定点修饰、原位可控聚合,以及SCIP在生物医学领域的应用等几个方面详细介绍SICP方法的研究进展,并对该方法未来的研发方向进行了简要的总结和展望.
