Synthesis of Cell-Recognizable Sugar-Peptide Conjugates by Living Ring-Opening Polymerization

通过开环聚合合成细胞可识别的糖肽缀合物

• 批准号: 07651081
• 负责人: OKADA Masahiko
• 金额: $ 1.41万
• 依托单位: Nagoya University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07651081/
• 关键词: Glycopeptide; Living Polyemrization; Ring-Opening Polymerization; Block Copolymer; Graft Copolymer; Molecular Recognition; Functional Polymer; alpha-Amino Acid N-Carboxyanhydride (NCA); 糖ペプチド; 細胞認識; アミノ酸N-カルボキシ無水物; 糖鎖高分子; レクチン; N-アセチルグルコサミン

Well-defined glycopeptide-containing block copolymers were synthesized by ring-opening polymerization of a sugar-substituted alpha-amino acid N-carboxyanhydride (NCA), i.e., O-(tetra-O-acetyl-beta-D-gluco-pyranosyl)-L-serine NCA (1), initiated with omega-amine-terminated poly (2-methyl-2-oxazoline) and poly (2-phenyl-2-oxazoline) macroinitiators in dichloromethane at 27ﾟC.DPs of peptide segments of the resulting poly (2-methyl-2-oxazoline)-block-poly [O-(tetra-O-acetyl-beta-D-glucopyranosyl)-L-serine](2a) and poly (2-phenyl-2-oxazoline)-block-poly [O-(tetra-O-acetyl-beta-D-glucopyranosyl)-L-serine](2b) were close to monomer/macroinitiator feed molar ratios. Glycopeptide-bearing block copolymers, poly (2-methyl-2-oxazoline)-block-poly [O-(beta-D-glucopyranosyl)-L-serine] and poly (2-phenyl-2-oxazoline)-block-poly [O-(beta-D-glucopyranosyl)-L-serine], were derived from 2a and 2b, respectively, by deacetylation with hydrazine monohydrate.First synthesis of well-defined glycopeptide macromonomers with an alpha-styryl group was performed by living ring-opening polymerization of sugar-substituted NCAs, i.e., 1 and O-(2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-beta-D-glucopyranosyl)-L-serine NCA,followed by deacetylation with hydrazine monohydrate in methanol at 0ﾟC.Water-soluble copolymer between the macromonomer and acrylamide was obtained by the radical copolymerization with 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPD) as an initiator in water at 55ﾟC.

采用开环聚合法制备糖取代的α -氨基酸n -羧基氢化物（NCA），即O-（四-O-乙酰- β -d -葡萄糖-吡喃基）- l-丝氨酸NCA(1)，以ω -胺端聚（2-甲基-2-恶唑啉）和聚（2-苯基-2-恶唑啉）大引发剂在27℃的二氯甲烷中引发，合成了定义良好的含糖肽嵌段共聚物。所得聚（2-甲基-2-恶唑啉）-嵌段聚[O-（四-O-乙酰- β - d -葡萄糖吡喃基）- l-丝氨酸]（2a）和聚（2-苯基-2-恶唑啉）-嵌段聚[O-（四-O-乙酰- β - d -葡萄糖吡喃基）- l-丝氨酸]（2b）的肽段dp接近单体/大引发剂投料摩尔比。通过与一水合肼的脱乙酰化，分别从2a和2b中得到了含糖肽的嵌段共聚物聚（2-甲基-2-恶唑啉）-嵌段聚[O-（β - d -葡萄糖吡喃基）- l-丝氨酸]和聚（2-苯基-2-恶唑啉）-嵌段聚[O-（β - d -葡萄糖吡喃基）- l-丝氨酸]。首先通过糖取代的NCA（1 -（2-乙酰氨基-3,4,6-三-O-乙酰基-2-脱氧- -d -葡萄糖吡喃基）- l-丝氨酸NCA）的活开环聚合，合成了具有明确定义的糖肽大单体，然后与一水合肼在0 / h / C甲醇中脱乙酰化。以2,2′-偶氮（2-氨基丙烷）二盐酸（AAPD）为引发剂，在55℃的水溶液中进行自由基共聚，得到了丙烯酰胺与大单体的水溶性共聚物。

项目成果

K.Aoi: "First Synthesis of Glycopeptide Macromonomers and Graft-Type Sugar-Containing Polymers with Glycopeptide Side Chains" Macromolecules. 29(12). 4456-4458 (1996)

K.Aoi：“糖肽大单体和具有糖肽侧链的接枝型含糖聚合物的首次合成”大分子。

K.Naka: "Aggregates of Peptide-Containing Block Copolymers and their Interactions with Lipase in Aqueous Solution" Macromolecular Chemistry and Physics. 198(1). 89-100 (1997)

K.Naka：“含肽嵌段共聚物的聚集体及其与水溶液中脂肪酶的相互作用”高分子化学和物理。

K. Naka: "Aggregates of Peptide-Containing Block Copolymers and their Interactions with Lipase in Aqueous Solution" Macromolecular Chemistry and Physics. 198(1). 89-100 (1997)

K. Naka：“含肽嵌段共聚物的聚集体及其与水溶液中脂肪酶的相互作用”高分子化学和物理。

Aoi,K.et al.: "Miscibility of Poly(vinyl chloride)with Chitin Derivatives Having Poly(2-methyl-2-oxazoline)Side Chains." Macromolecular Rapid Communication. 16. 53-58 (1995)

Aoi,K.et al.：“聚（氯乙烯）与具有聚（2-甲基-2-恶唑啉）侧链的甲壳素衍生物的混溶性。”

M.Okada: Glycoproteins (Synthesis by NCA Method). Polymeric Materials Encyclopedia, 9218 (1996)

M.Okada：糖蛋白（通过 NCA 方法合成）。