在体外选择的原结合性血管内皮生长因子含有遗传编码的贝灵感的粘合性氨基酸
Takuya Miwa1,2,3,4, Akiko Yumoto5, Seiichi Tada5
1Nano Medical Engineering Laboratory, RIKEN Cluster for Pioneering Research, 2-1 Hirosawa, Wako, Saitama, 351-0198, Japan.
Chemistry (Weinheim an der Bergstrasse, Germany)
|January 10, 2025
概括
研究人员开发了一种新的粘合蛋白,DOPA含有原结合血管内皮生长因子 (CB-VEGF),使用体外选择和鱼灵感的氨基酸. 这种蛋白质增强了原表面的细胞生长,显示出医疗和工业应用的前景.
科学领域:
- 生物技术是生物技术.
- 蛋白质工程是指蛋白质工程.
- 生物材料科学 生物材料科学
背景情况:
- 蛋白质固定对于医疗和工业应用至关重要.
- 以前的方法确定了原结合性血管内皮生长因子 (CB-VEGF),但受到正规氨基酸的限制.
- 海洋的粘合蛋白激发了非天然氨基酸的结合.
研究的目的:
- 将粘合性非天然氨基酸L-3,4-二基氨 (DOPA) 纳入CB-VEGF以增强蛋白质粘附.
- 评估含有DOPA的CB-VEGF的原蛋白结合特性和协同效应.
- 评估CB-VEGF对原表面细胞生长的影响.
主要方法:
- 采用"全在一"的体外选择,从融合库中识别含有DOPA的CB-VEGF.
- 使用明显解离常数对原结合亲和力的表征.
- 对含有DOPA的酸与DOPA突变的酸 (氨酸替代) 的比较分析.
- 对CB-VEGF与VEGF处理的原表面细胞增殖的评估.
主要成果:
- 一种含有DOPA的CB-VEGF被成功鉴定为具有强烈的原结合 (明显解离常数为2nM).
- DOPA残留对原结合至关重要,正如DOPA突变中的结合较弱所证明的那样.
- CB-VEGF表现出协同的原结合效应,明显强于其成分的添加功能.
- 与未经处理或VEGF处理的表面相比,CB-VEGF对原表面的处理促进了细胞生长的增加.
结论:
- 将全合一的体外选择与DOPA结合相结合是工程粘合蛋白的有希望的策略.
- 含有DOPA的CB-VEGF表现出增强的原结合亲和力,并促进细胞生长,表明生物材料开发的潜力.
- 这种方法提供了一种创新的方法,用于创建功能化的基于蛋白质的生物材料,用于各种应用.
相关概念视频
Paracrine Signaling
Paracrine signaling allows cells to communicate with their immediate neighbors via secretion of signaling molecules. Such a signal can only trigger a response in nearby target cells because the signal molecules degrade quickly or are inactivated if not taken up. Prominent examples of paracrine signaling include nitric oxide signaling in blood vessels, synaptic signaling of neurons, the blood clotting system, tissue repair/wound healing, and local allergic skin reactions. Nitric oxide as a...
Regulation of Angiogenesis and Blood Supply
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...
Fibronectins Connect Cells with ECM
Fibronectin is an adhesive glycoprotein present in the extracellular matrix of embryogenic and adult tissue. These molecules primarily aid in regulating cell motility and attachment. A fibronectin molecule is composed of two identical polypeptide chains attached to each other by a pair of disulfide bonds at the C-terminal.
Both proteoglycans and collagen are attached to fibronectin proteins, which, in turn, are attached to integrin proteins. These integrin proteins interact with transmembrane...
Both proteoglycans and collagen are attached to fibronectin proteins, which, in turn, are attached to integrin proteins. These integrin proteins interact with transmembrane...
Integrins
Animal and protozoan cells do not have cell walls to help maintain shape and provide structural stability. Instead, these eukaryotic cells secrete a sticky mass of carbohydrates and proteins into the spaces between adjacent cells. This network of proteins and molecules is called an extracellular matrix or ECM.
Some ECM proteins assemble into a basement membrane to which the remaining components adhere. Proteoglycans typically form the bulk of the ECM while fibrous proteins, like collagen,...
Some ECM proteins assemble into a basement membrane to which the remaining components adhere. Proteoglycans typically form the bulk of the ECM while fibrous proteins, like collagen,...
Selectins
Cell adhesion is an essential aspect of multicellularity. While stable cell interactions usually occur between cells of the same type, transient cell interactions occur between cells of different tissue types, such as between neutrophils and endothelial cells. Selectins are one class of cell adhesion molecules (CAMs) that bind carbohydrate ligands to form transient cell adhesion. They are rod-like proteins with a long extracellular part of variable length ending with the lectin domain, which...
Role of Hematopoietic Growth Factors
Hematopoietic growth factors are molecules that regulate the differentiation rate of hematopoietic stem cells (HSCs). Erythropoietin (EPO), primarily produced by the kidneys, plays a crucial role in erythrocyte production. When oxygen levels in the blood are low, EPO is released into the bloodstream, reaching the bone marrow, where it stimulates HSCs to differentiate and mature into erythrocytes, which are vital for oxygen transport.
Thrombopoietin (TPO), mainly released by the liver,...
Thrombopoietin (TPO), mainly released by the liver,...


