title: Characterization of poly-leucine substituted analogues of the human surfactant protein SP-C.
abstract: A series of novel amphipathic peptides constituted of an N-terminal hydrophilic portion (CPVHLKR, residues 6-12) of human pulmonary surfactant protein-C (SP-C) and a poly-leucine (poly-L) stretch of various chain lengths as the C-terminal hydrophobic tail were synthesized and evaluated relevant to their ability to improve the surface activity of a ternary lipid mixture composed of dipalmitoylphosphatidylcholine, egg-phosphatidylglycerol and palmitic acid (DPPC/E-PG/PA, 75:25:10, w/w) in a Langmuir-Wilhelmy surface balance. CPVHLKRL11, a human SP-C analogue bearing an 11-residue poly-L tail, and its related peptides with longer tails in the ternary lipid mixture, accelerated not only the surface spreading at the air-water interface but also exhibited significantly improved dynamic surface activity, compared to the ternary lipid mixture. Their surface activities were almost indiscernible from those of the synthetic human SP-C. When reconstituted into a ternary lipid mixture containing members of the homologous series of n-saturated diacylphosphatidylglycerol, the surface activities of the poly-L analogues were almost completely unaffected, whereas replica peptides carrying the hydrophobic portion of native SP-C were found to have distinct surface activities depending upon the acyl-chain lengths of phosphatidylglycerol. The poly-L stretch of a poly-L analogue could be replaced with poly-norleucine of the same chain length without a significant loss of surface activity. Substitution of the poly-L portion in the analogues with poly-valine or poly-isoleucine resulted in a considerable decrease in surface activity. The poly-L analogue in the DPPC/E-PG/PA mixture was demonstrated to act as an excellent surfactant comparable with Surfacten, a modified bovine surfactant preparation that was used for treatment for infant respiratory distress syndrome, based on evaluation of the lung pressure-volume characteristics using premature rabbit neonates.
authors.affiliation: Department of Biochemistry, Faculty of Science, Saitama University, Urawa, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Takei
authors.forename: Y
authors.initials: Y
authors.lastname: Hashimoto
authors.forename: E
authors.initials: E
authors.lastname: Ohtsubo
authors.forename: K
authors.initials: K
authors.lastname: Sakai
authors.forename: H
authors.initials: H
authors.lastname: Ohkawa
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D055592:Biophysical Phenomena; D001703:Biophysics; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D005260:Female; D006801:Humans; D008055:Lipids / Q000737:chemistry; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D011247:Pregnancy; D011510:Proteolipids / Q000138:chemical synthesis / Q000737:chemistry*; D011663:Pulmonary Surfactants / Q000138:chemical synthesis / Q000737:chemistry*; D011817:Rabbits; D013501:Surface-Active Agents / Q000138:chemical synthesis / Q000737:chemistry
chemical_list: D008055:Lipids; D010455:Peptides; D011510:Proteolipids; D011663:Pulmonary Surfactants; D013501:Surface-Active Agents; C027819:polyleucine