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海藻糖功能化糖肽增强无甘油冷冻保存红细胞。

Trehalose-functional glycopeptide enhances glycerol-free cryopreservation of red blood cells.

机构信息

School of Materials Science and Engineering, and Tianjin Key Laboratory of Composite and Functional Materials, Tianjin University, Tianjin 300350, China.

出版信息

J Mater Chem B. 2019 Sep 25;7(37):5695-5703. doi: 10.1039/c9tb01089k.

DOI:10.1039/c9tb01089k
PMID:31482162
Abstract

The long-term cryopreservation of cells, tissues and organs is limited by both osmotic stress and ice injury during freezing or thawing. Introduction of biocompatible cryoprotective agents is promising for cell cryopreservation based on membrane stabilization of glycopeptides and trehalose. Herein, a series of trehalose-functional (glyco)peptides were synthesized by successively tethering Nω-(4-toluenesulfonyl)-l-arginine and carboxylated trehalose to the side amino groups of ε-polylysine. The specifically synthesized glycopeptide demonstrated enhanced cryosurvival of sheep red blood cells (RBCs) from 49.1 ± 0.9% to 75.0 ± 2.4% at pH 7.4, along with trehalose molecules. Cryopreservation via membrane stabilization was proposed such that the glycopeptide could attach on the cell membrane surface of RBCs to protect the cell membrane from osmotic injury by electrostatic interactions, π-π stacking and hydrogen bonding. Meanwhile, trehalose could prevent RBCs from ice injury via ice recrystallization inhibition activity. Thus, membrane protection for preventing osmotic stress and ice injury could be boosted via synergistic interaction between the glycopeptide and trehalose. The combined usage of biocompatible glycopeptides and trehalose could potentially be applied in the glycerol-free cryopreservation of cells and tissues in biomedicine.

摘要

细胞、组织和器官的长期低温保存受到冷冻或解冻过程中渗透应激和冰晶损伤的限制。基于糖肽和海藻糖对细胞膜的稳定作用,引入生物相容性的低温保护剂有望用于细胞低温保存。在此,通过将 Nω-(4-甲苯磺酰基)-l-精氨酸和羧基化海藻糖依次连接到 ε-聚赖氨酸的侧氨基上,合成了一系列海藻糖功能(糖)肽。在 pH 值为 7.4 时,特定合成的糖肽与海藻糖分子一起,将绵羊红细胞 (RBC) 的冷冻存活率从 49.1±0.9%提高到 75.0±2.4%。通过膜稳定进行冷冻保存的机制是糖肽可以附着在 RBC 的细胞膜表面,通过静电相互作用、π-π 堆积和氢键来保护细胞膜免受渗透损伤。同时,海藻糖可以通过抑制冰晶重结晶来防止 RBC 受到冰损伤。因此,糖肽和海藻糖之间的协同相互作用可以增强膜保护,以防止渗透应激和冰损伤。生物相容性糖肽和海藻糖的联合使用可能有望应用于生物医学中无甘油的细胞和组织的冷冻保存。

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