Department of Pediatrics, David Geffen School of Medicine, University of California Los Angeles, 405 Hilgard Avenue, Los Angeles, CA, 90095, USA.
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, 1124 West Carson Street, Torrance, CA, 90502, USA.
BMC Pulm Med. 2021 Oct 22;21(1):330. doi: 10.1186/s12890-021-01695-0.
Optimal functionality of synthetic lung surfactant for treatment of respiratory distress syndrome in preterm infants largely depends on the quality and quantity of the surfactant protein B (SP-B) peptide mimic and the lipid mixture. B-YL peptide is a 41-residue sulfur-free SP-B mimic with its cysteine and methionine residues replaced by tyrosine and leucine, respectively, to enhance its oxidation resistance.
Testing the structural and functional stability of the B-YL peptide in synthetic surfactant lipids after long-term storage.
The structural and functional properties of B-YL peptide in surfactant lipids were studied using three production runs of B-YL peptides in synthetic surfactant lipids. Each run was held at 5 °C ambient temperature for three years and analyzed with structural and computational techniques, i.e., MALDI-TOF mass spectrometry, ATR-Fourier Transform Infrared Spectroscopy (ATR-FTIR), secondary homology modeling of a preliminary B-YL structure, and tertiary Molecular Dynamic simulations of B-YL in surfactant lipids, and with functional methods, i.e., captive bubble surfactometry (CBS) and retesting in vivo surface activity in surfactant-deficient young adult rabbits.
MALDI-TOF mass spectrometry showed no degradation of the B-YL peptide as a function of stored time. ATR-FTIR studies demonstrated that the B-YL peptide still assumed stable alpha-helical conformations in synthetic surfactant lipids. These structural findings correlated with excellent in vitro surface activity during both quasi-static and dynamic cycling on CBS after three years of cold storage and in vivo surface activity of the aged formulations with improvements in oxygenation and dynamic lung compliance approaching those of the positive control surfactant Curosurf®.
The structure of the B-YL peptide and the in vitro and in vivo functions of the B-YL surfactant were each maintained after three years of refrigeration storage.
合成肺表面活性剂治疗早产儿呼吸窘迫综合征的最佳功能在很大程度上取决于表面活性蛋白 B（SP-B）肽模拟物的质量和数量以及脂质混合物。B-YL 肽是一种 41 个残基的无硫 SP-B 模拟物，其半胱氨酸和蛋氨酸残基分别被酪氨酸和亮氨酸取代，以增强其抗氧化能力。
测试 B-YL 肽在长期储存后合成表面活性剂脂质中的结构和功能稳定性。
使用三种生产批次的 B-YL 肽在合成表面活性剂脂质中研究 B-YL 肽在表面活性剂脂质中的结构和功能特性。每个批次在 5°C 环境温度下储存三年，并使用结构和计算技术进行分析，即基质辅助激光解吸/电离飞行时间质谱（MALDI-TOF MS）、衰减全反射傅里叶变换红外光谱（ATR-FTIR）、初步 B-YL 结构的二级同源建模以及 B-YL 在表面活性剂脂质中的三级分子动力学模拟，以及功能方法，即俘获泡表面张力仪（CBS）和在缺乏表面活性剂的年轻成年兔体内重新测试表面活性。
MALDI-TOF MS 显示 B-YL 肽的降解与储存时间无关。ATR-FTIR 研究表明，B-YL 肽在合成表面活性剂脂质中仍保持稳定的α-螺旋构象。这些结构发现与在冷藏储存三年后的 CBS 上进行的准静态和动态循环的优异体外表面活性以及老化配方的体内表面活性相关，其氧合和动态肺顺应性的改善接近阳性对照表面活性剂 Curosurf®。
B-YL 肽的结构以及 B-YL 表面活性剂的体外和体内功能在冷藏储存三年后均得到维持。
