The Surface Properties of Chemically Synthesized Peptides Analogous to Human Pulmonary Surfactant Protein SP-C

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A number of peptides with different lengths corresponding to various regions of human pulmonary surfactant protein SP-C were synthesized and their activity evaluated to improve in vitro surface activities and in situ lung pressure-volume characteristics of a ternary lipid mixture composed of dipalmitoylphosphatidylcholine, phosphatidylglycerol and palmitic acid (75 : 25 : 10, w/w). SP-C (1-35), a synthetic peptide with the entire length of human SP-C, and some other peptides with various lengths of its partial sequences were remarkably active. All of these peptides shared a common core sequence of (C)CPVHLKRLLIVVVVVVLIVVVIVGAL(L). Any deletion in this core sequence resulted in reduction of activity of the peptide. SP-C (5-31) and SP-C (6-32), the minimum peptides containing the core sequence, were combined with the ternary lipid mixture at the final peptide concentration of 2% (w/w) into synthetic surfactants which showed excellent properties comparable with those of Surfacten^[○!R], a commercially available modified bovine lung surfactant. In a Langmuir-Wilhelmy surface balance, the synthetic surfactant containing SP-C (6-32) spread and adsorbed quickly to reach a surface tension of 30.8 mN/m at 30-s spreading time and 41.2 mN/m at 1-min adsorption time, respectively; the presence of SP-C (6-32) significantly prevented the decrease of surface activity of the ternary lipid mixture during dynamic compression-expansion cycles. Furthermore, tracheal instillation of the synthetic surfactant containing SP-C (6-32) at the dose of 50 mg of phospholipids/kg improved lug pressure-volume characteristics of immature rabbit neonates to a level similar to that of mature neonates at term.