The use of synthetic peptides in the formation of biophysically and biologically active pulmonary surfactants.
Synthetic pulmonary surfactants consisting of mixtures of phospholipids with synthetic peptides based on the amino acid sequence of human surfactant apoprotein SP-B were prepared. These surfactants were analyzed for their ability to lower surface tension on a pulsating bubble surfactometer and for their capacity to improve lung compliance and increase alveolar expansion in a fetal rabbit model of surfactant deficiency. The data demonstrate that several peptides, ranging from 17 to 45 residues in length, matching the carboxy-terminal sequence of the SP-B protein, when appropriately recombined with the phospholipid dipalmitoylphosphatidylcholine and phosphatidylglycerol (3:1), are capable of producing a synthetic surfactant with biophysical and biologic activity approaching that of human surfactant derived from amniotic fluid.
Revak
S D
SD
Department of Immunology, Research Institute of Scripps Clinic, La Jolla, California 92037.
Merritt
T A
TA
Hallman
M
M
Heldt
G
G
La Polla
R J
RJ
Hoey
K
K
Houghten
R A
RA
Cochrane
C G
CG
D015060:1,2-Dipalmitoylphosphatidylcholine; D000595:Amino Acid Sequence; D000818:Animals; D001059:Apoproteins / Q000138:chemical synthesis* / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000196:embryology*; D008170:Lung Compliance / Q000187:drug effects*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis* / Q000494:pharmacology; D010715:Phosphatidylglycerols; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000138:chemical synthesis* / Q000494:pharmacology; D011817:Rabbits / Q000196:embryology; D013500:Surface Tension
D001059:Apoproteins; D010446:Peptide Fragments; D010715:Phosphatidylglycerols; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; C046616:pulmonary surfactant apoprotein; D015060:1,2-Dipalmitoylphosphatidylcholine