A synthetic segment of surfactant protein A: structure, in vitro surface activity, and in vivo efficacy.
Surfactant protein A (SP-A) is a 248-residue, water-soluble, lipid-associating protein found in lung surfactant. Analysis of the amino acid sequence using the Eisenberg hydrophobic moment algorithm predicts that the SP-A segment spanning residues 114-144 has high hydrophobic moments, typical of lipid-associating amphipathic domains. The secondary structure, in vitro surface activity and in vivo lung activity of this SP-A sequence were studied with a 31-residue synthetic peptide analog (A114-144). Analysis of the secondary structure using circular dichroism and Fourier transform infrared spectroscopy indicated association with lipid dispersions and a dominant helical content. Surface activity measurements of A114-144 with surfactant lipid dispersions and the hydrophobic surfactant proteins B and C (SP-B/C) showed that A114-144 enhances surface activity under conditions of dynamic compression and respreading on a Langmuir/Wilhelmy surface balance. Synthetic surfactant dispersions containing A114-144 improved lung compliance in spontaneously breathing, 28-d premature rabbits to a greater degree than surfactant dispersions with synthetic SP-B/C and synthetic surfactant lipids alone. These observations indicate that inclusion of A114-144 may improve synthetic preparations currently used for surfactant replacement therapy.
Walther
F J
FJ
Department of Pediatrics, Martin Luther King, Jr./Drew University Medical Center, Los Angeles, California 90059, USA.
David-Cu
R
R
Leung
C
C
Bruni
R
R
Hernández-Juviel
J
J
Gordon
L M
LM
Waring
A J
AJ
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D005260:Female; D050356:Lipid Metabolism; D008168:Lung / Q000196:embryology / Q000378:metabolism; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D011510:Proteolipids / Q000737:chemistry* / Q000378:metabolism*; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000737:chemistry* / Q000378:metabolism*; D011817:Rabbits
D011510:Proteolipids; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants