Encinas-Basurto David, Muralidharan Priya, Saiful Islam M D, Vallorz Ernest L, Black Stephen M, Kraft Monica, Ledford Julie G, Mansour Heidi M
The University of Arizona College of Pharmacy Tucson AZ USA.
University of Sonora Mexico.
RSC Pharm. 2025 May 6. doi: 10.1039/d4pm00265b.
Surfactant protein-A (SP-A) is an endogenous and essential lung surfactant-specific protein that is integral to pulmonary immunity, including inhibition of asthma exacerbations. This study aims to comprehensively characterize two peptides (10-AA and 20-AA) of SP-A which confer activity similar to the full-length oligomeric SP-A protein. Spectroscopic and chromatographic analyses revealed that the phosphate (PS) and acetate (AC) salts exhibited distinct solubility and log partitioning behavior, impacting their physicochemical properties. MD simulations and circular dichroism showed that SP-A 10-AA initially adopts an α-helical structure but loses helicity over time, while SP-A 20-AA remains disordered. Differential scanning calorimetry confirmed variations in thermal stability between salt forms and zeta potential measurements showed that PS salts had a more negative surface charge, potentially influencing membrane interactions. studies showed high cell viability (>90%) and stable TEER values at the air-liquid interface, confirming biocompatibility and potential epithelial permeability. These findings provide crucial insights into the structural and functional properties of SP-A peptides, supporting their potential as therapeutic agents for pulmonary diseases.
表面活性蛋白-A（SP-A）是一种内源性且必需的肺表面活性物质特异性蛋白，对肺部免疫至关重要，包括抑制哮喘发作。本研究旨在全面表征SP-A的两种肽段（10个氨基酸和20个氨基酸），它们具有与全长寡聚体SP-A蛋白相似的活性。光谱和色谱分析表明，磷酸盐（PS）盐和醋酸盐（AC）盐表现出不同的溶解性和对数分配行为，影响其物理化学性质。分子动力学模拟和圆二色性表明，SP-A 10个氨基酸最初采用α-螺旋结构，但随时间失去螺旋性，而SP-A 20个氨基酸仍保持无序状态。差示扫描量热法证实了盐形式之间热稳定性的差异，ζ电位测量表明PS盐具有更负的表面电荷，可能影响膜相互作用。研究表明，在气液界面处细胞活力高（>90%）且跨上皮电阻值稳定，证实了生物相容性和潜在的上皮通透性。这些发现为SP-A肽的结构和功能特性提供了关键见解，支持了它们作为肺部疾病治疗药物的潜力。
