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, liquid-as sociating protein found in lung surfactant. Analysis of the amino acid sequence using the Eisenberg hydrophobic moment algorithm predicts th at the SP-A segment spanning residues 114-444 has high hydrophobic mom ents, 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 ii-residue synthetic peptide analog (A(114-144)). Analysis of the secondary structure using circular dich roism and Fourier transform infrared spectroscopy indicated associatio n with lipid dispersions and a dominant helical content. Surface activ ity measurements of A(114-144) With surfactant lipid dispersions and t he hydrophobic surfactant proteins B and C (SP-B/C) showed that A(144- 144) enhances surface activity under conditions of dynamic compression and respreading on a Langmuir/Wilhelmy surface balance, Synthetic sur factant dispersions containing A(144-144) improved lung compliance in spontaneously breathing, 28-d premature rabbits to a greater degree th an surfactant dispersions with synthetic SP-B/C and synthetic surfacta nt lipids alone. These observations indicate that inclusion of A(114-1 44) may improve synthetic preparations currently used for surfactant r eplacement therapy.