GAG (glycosaminoglycan) analogue realizing cell membrane modification, synthetic method of GAG analogue and application method of GAG analogue in in-vitro induced stem cell directional differentiation

Abstract

The invention discloses a GAG (glycosaminoglycan) analogue realizing cell membrane modification, a synthetic method of the GAG analogue and an application method of the GAG analogue in in-vitro induced stem cell directional differentiation. The GAG analogue can be inserted into the surface of a cell membrane and can prompt a stem cell to be directionally and efficiently differentiated into a mature neuronal cell in a shorter cycle. The phospholipid anchored GAG analogue is prepared firstly through RAFT (reversible addition-fragmentation chain transfer) polymerization, and then phospholipidation of the GAG analogue is realized through maleimidized lipid molecules; the phospholipidized GAG analogue is introduced to the surface of the stem cell through affinity interaction between phospholipid groups and the cell membrane, so that the stem cell can be better prompted to be efficiently differentiated into the mature neuronal cell. A synthetic process is simple, and a powerful means capable of realizing phospholipidation of almost every RAFT polymer is provided.

Description

technical field [0001] The invention belongs to the fields of small molecules, polymer synthesis and biomedical applications, and in particular relates to a maleimidated phospholipid molecule, a green fluorescein-labeled glycosaminoglycan analog, and a phospholipid-anchored glycosaminoglycan analog The synthesis method of the substance uses the reaction between chemically active groups and RAFT technology to obtain a polymer substance that can be inserted into the cell membrane and can efficiently promote the directional differentiation of embryonic stem cells into mature neurons in a short period of time. Background technique [0002] Embryonic stem cells (ESCs) are a type of totipotent cells isolated from the inner cell mass of the blastocyst stage, which can self-renew and differentiate into almost all somatic cells under certain conditions. Promising cell source for cell therapy and tissue transplantation. Natural glycosaminoglycan (GAG) is a highly structurally heterog...

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Problems solved by technology

However, whether it is natural GAG molecules or chemically synthesized GAG analogs, although they can obtain certain biological activities in the process of interacting with cells, these polymer molecules will be internalized by cells in a short time, making functional Polymer molecules cannot directly interact with specific growth factors and corresponding receptors on the cell surface. Therefore, a phospholipid group-anchored GAG analog is prepared by cell membrane surface engineering technology, and GAG The analogs are directly introduced into the cell membrane to induce the differentiation of ESCs, and its application in tissue engineering has important scientific value and social significance

[0003] At present, the main method for preparing GAG analogs anchored by phospholipid groups is as follows: first, synthesize a RAFT reagent containing phospholipid groups (the commonly used molecule is DPPE), and then carry out RAFT polymerization of vinyl monomers with a certain structure to obtain A polymer with a phospholipid group at the end of the molecular chain. Finally, a monosaccharide or disaccharide molecule of a specific structure is grafted onto the polymer chain through a chemical reaction to obtain a polysaccharide molecule anchored by the phospholipid group. Although this method can The biological activities of different types of GAGs are obtained, but their derivatives based on natural structural sugars lead to uncontrollable sulfonation degrees on the main chain, and the preparation process often involves the subsequent introduction of fluorescent groups and deprotection processes, making synthesis and The purification process is complicated, which limits the wide application of this method

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