Stability and structure-activity relationship of the SPA4 peptide under ambient and stressed conditions of lung injury.
Stability and structure-activity relationship of the SPA4 peptide under ambient and stressed conditions of lung injury.
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肺部炎症和损伤是主要的健康问题。SPA 4肽（氨基酸序列GDFRYSDGTPVNYTNWYRGE）结合Toll样受体-4并发挥抗炎活性。在这项研究中，我们已经确定了SPA 4肽在肺损伤的环境和应激条件下的结构稳定性和构效关系。将SPA 4肽保持在不同pH和温度下，在不同离子强度的溶液和模拟肺液中。通过紫外-可见（UV-VIS）和圆二色性（CD）光谱测定SPA 4肽的一级和二级结构。通过测量原代小鼠肺上皮细胞对脂多糖（LPS）刺激的趋化因子C-X-C基序配体1/角化细胞衍生的趋化因子（CXCL 1/KC）和乳酸的分泌水平来确定SPA 4肽的活性。我们的结果证明了SPA 4肽的结构在室温和4 °C下在10天内的稳定性。SPA 4肽的原始UV-VIS光谱在不同温度下在pH 5.7、7.0和8.0的溶液、模拟肺液和大多数化学成分中孵育时遵循典型模式。在某些条件下，在SPA 4肽的四阶导数光谱中注意到吸收峰、导数值和振动精细结构的轻微位移。乳酸水平升高是肺损伤的标志。SPA 4肽本身和在乳酸盐存在下发挥抗炎活性。当在2 mM乳酸钠溶液中预孵育时，SPA 4肽的一级和二级结构以及活性保持完整。这些结果为SPA 4肽的稳定性和构效关系提供了重要的见解。本文介绍的工作描述了SPA 4肽在环境条件、模拟肺液和化学成分中的结构，以及SPA 4肽对抗脂多糖刺激的构效关系。
Lung inflammation and injuries are major health problems. The SPA4 peptide (amino acid sequence GDFRYSDGTPVNYTNWYRGE) binds to Toll-like receptor-4 and exerts anti-inflammatory activity. In this study, we have determined the stability of the structure and structure–activity relationship of the SPA4 peptide under ambient and stressed conditions of lung injury. The SPA4 peptide was maintained at different pH and temperatures, in solutions of different ionic strengths, and simulated lung fluids. The primary and secondary structure of the SPA4 peptide was determined by ultraviolet-visible (UV-VIS) and circular dichroism (CD) spectroscopy. The activity of the SPA4 peptide was determined by measurement of secreted levels of chemokine C–X–C motif ligand 1/keratinocyte-derived chemokine (CXCL1/KC) and lactate by primary mouse lung epithelial cells against lipopolysaccharide (LPS) stimuli. Our results demonstrate the stability of the structure of the SPA4 peptide at room temperature and 4 °C over 10 days. The original UV-VIS spectra of the SPA4 peptide followed a typical pattern when incubated in solutions of pH 5.7, 7.0, and 8.0 at different temperatures, simulated lung fluids, and most of the chemical components. Slight shifts in the absorbance peaks, derivative values, and vibrational fine structures were noted in the fourth-derivative spectra of the SPA4 peptide under some conditions. An increased level of lactate is the hallmark of lung injury. The SPA4 peptide on its own and in the presence of lactate exerts anti-inflammatory activity. The primary and secondary structure and the activity of the SPA4 peptide remain intact when pre-incubated in 2 mM sodium lactate solution. The results provide important insights about the stability and structure–activity relationship of the SPA4 peptide. Presented work in this article describes the structure of SPA4 peptide in ambient conditions, simulated lung fluids and chemical components, and structure–activity relation of SPA4 peptide against lipopolysaccharide stimuli.
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SPA4肽对人类细胞系统和肺损伤小鼠模型中脂多糖破坏的肺上皮屏障的影响。
影响因子：
2.5
作者：
通讯作者：
--
影响因子：
3.7
作者：
Brown, SD;Clark, C;Gutierrez, G
通讯作者：
Gutierrez, G
影响因子：
15
作者：
KANAVARIOTI, A;BERNASCONI, CF;ALBERAS, DJ
通讯作者：
ALBERAS, DJ
DOI：
10.7759/cureus.26229
发表时间：
2022-06
期刊：
Cureus
影响因子：
--
作者：
Makwana S;Patel A;Sonagara M
通讯作者：
Sonagara M
影响因子：
3.9
作者：
Garcia-Sanz, Maria-Teresa;Martinez-Gestoso, Sandra;Gonzalez-Barcala, Francisco-Javier
通讯作者：
Gonzalez-Barcala, Francisco-Javier