Characterization of Poly-Leucine Substituted Analogues of the Human Surfactant Protein SP-C

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概要

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• 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. CPVHLKRL_<11>, 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 Surfactan^<[○!R]>, 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.

• 公益社団法人日本薬学会の論文
• 1996-12-15

著者

• OHKAWA Hiroshi

  Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi

• Ohkawa Hiroshi

  Interdisciplinary Graduate School Of Medicine And Engineering University Of Yamanashi

• Ohkawa Hiroshi

  Research Laboratories R & D Division Tokyo Tanabe Co. Ltd.

• Hashimoto Y

  Graduate School Of Pharmaceutical Sciences Kyushu University

• SAKAI Kayo

  Department of Biochemistry, Kyoto Pharmaceutical University

• SAKAI Kaoru

  Research Laboratories, Mitsubishi Pharma Co. Ltd.

• Hashimoto Yohichi

  Department of Biochemistry, Faculty of Science, Saitama University

• TAKEI Tsunetomo

  Research Center, Mitsubishi Pharma Corporation

• Takei T

  Research Center Mitsubishi Pharma Corporation

• Takei Tsunetomo

  Department Of Pediatrics School Of Medicine Iwate Medical University

• Sakai K

  Nippon Beohringer Ingelheim Co. Ltd. Hyogo Jpn

• OHTSUBO Eiji

  Research Laboratories, R & D Division, Tokyo Tanabe Co., Ltd.,

• Ohtsubo Eiji

  Research Laboratories R & D Division Tokyo Tanabe Co. Ltd.

• Takei Tsunemoto

  Department of Biochemistry, Faculty of Science, Saitama University

• Hashimoto Yoichi

  Department of Biochemistry, Faculty of Science, Saitama University

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