The surface properties of chemically synthesized peptides analogous to human pulmonary surfactant protein SP-C.
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, 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 lung pressure-volume characteristics of immature rabbit neonates to a level similar to that of mature neonates at term.
Takei
T
T
Department of Biochemistry, Faculty of Science, Saitama University, Urawa, Japan.
Hashimoto
Y
Y
Aiba
T
T
Sakai
K
K
Fujiwara
T
T
D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000494:pharmacology; D002417:Cattle; D004338:Drug Combinations; D005233:Fatty Alcohols / Q000494:pharmacology; D006801:Humans; D055666:Lipopeptides; D008168:Lung / Q000187:drug effects; D008176:Lung Volume Measurements; D008969:Molecular Sequence Data; D010456:Peptides, Cyclic; D010767:Phosphorylcholine; D011092:Polyethylene Glycols / Q000494:pharmacology; D011510:Proteolipids / Q000138:chemical synthesis* / Q000494:pharmacology; D011663:Pulmonary Surfactants / Q000138:chemical synthesis* / Q000494:pharmacology; D011817:Rabbits; D013499:Surface Properties
D001426:Bacterial Proteins; D004338:Drug Combinations; D005233:Fatty Alcohols; D055666:Lipopeptides; D010456:Peptides, Cyclic; D011510:Proteolipids; D011663:Pulmonary Surfactants; D010767:Phosphorylcholine; C009365:surfactin peptide; D011092:Polyethylene Glycols; C047049:dipalmitoylphosphatidylcholine, hexadecanol, tyloxapol drug combination