申请人:Stichting Katholieke Universiteit, Radboud
Universiteit Nijmegen
公开号:EP2826493A8
公开(公告)日:2015-03-18
The invention relates to a process for making an oligo(alkylene glycol) functionalized co-polyisocyanopeptide, wherein the process comprises the steps of:
i) copolymerizing
- a first comonomer of an oligo(alkylene glycol) functionalized isocyanopeptide grafted with a linking group and
- a second comonomer of a non-grafted oligo(alkylene glycol) functionalized isocyanopeptide,
wherein the molar ratio between the first comonomer and the second comonomer is 1:500 and 1:30 and
ii) adding a reactant of a spacer unit and a cell adhesion factor to the copolymer obtained by step i), wherein the spacer unit is represented by general formula A-L-B, wherein the linking group and group A are chosen to react and form a first coupling and the cell adhesion factor and group B are chosen to react and form a second coupling, wherein the first coupling and the second coupling are independently selected from the group consisting of alkyne-azide coupling, dibenzocyclooctyne-azide coupling, oxanorbornadiene-based-azide couplings, vinylsulphone-thiol coupling, maleimide-thiol coupling, methyl methacrylate-thiol coupling, ether coupling, thioether coupling, biotin-strepavidin coupling, amine-carboxylic acid resulting in amides linkages, alcohol-carboxylic acid coupling resulting in esters linkages and NHS-Ester (N-Hydroxysuccinimide ester)-amine coupling and
wherein group L is a linear chain segment having 10-60 bonds between atoms selected from C, N, O and S in the main chain.
该发明涉及一种制备寡聚(烷基二醇)官能化共聚异氰酸肽的方法,其中该方法包括以下步骤:i)共聚合- 具有连接基团的寡聚(烷基二醇)官能化异氰酸肽的第一共聚单体和- 未嫁接的寡聚(烷基二醇)官能化异氰酸肽的第二共聚单体,其中第一共聚单体和第二共聚单体之间的摩尔比为1:500至1:30;和ii)向步骤i)得到的共聚物中添加一个间隔单元和细胞粘附因子的反应物,其中该间隔单元由一般式A-L-B表示,其中连接基团和基团A被选择用于反应形成第一偶联,细胞粘附因子和基团B被选择用于反应形成第二偶联,其中第一偶联和第二偶联分别选自炔基-叠氮偶联、二苯并环辛烯-叠氮偶联、氧杂环庚二烯基-叠氮偶联、乙烯磺酰基-硫醇偶联、马来亚酰胺-硫醇偶联、甲基丙烯酸甲酯-硫醇偶联、醚偶联、硫醚偶联、生物素-链霉素偶联、胺-羧酸生成酰胺键偶联、醇-羧酸偶联生成酯键和NHS-酯(N-羟基琥珀酰亚胺酯)-胺偶联,其中基团L是在主链中由C、N、O和S中的原子之间具有10-60个键的线性链段。