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

Abstract

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 P 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. In vitro 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.