Peptide-based synthetic pulmonary surfactant for the treatment of respiratory distress disorders

KL4 (sinapultide) represents the first peptide-based replacement for surfactant protein B in pulmonary surfactant (PS) therapies approved for clinical use. Surfaxin, its formulation with PS lipids, shows the promise of synthetic PS for replacing animal-derived PS in the treatment of respiratory distress syndromes and for treating acute lung injury. Efforts to characterize the molecular basis for KL4 function have revealed the peptide exhibits a helical structure which differentially partitions in response to both lipid saturation levels and pH. The penta-residue repeat of KL4 leads to adaptive peptide helicity, varying with partitioning depth, and suggests structural plasticity may represent an important mechanism for differential trafficking of lipids, particularly in intra-alveolar surfactant for the formation of stable DPPC monolayers at air-water interfaces.