Comprehensive physicochemical, biophysical, and characterization of lung surfactant SP-A peptidomimetics.

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.