Surfactant protein B and C analogues.
Mammalian lung surfactant is a mixture of phospholipids and four surfactant-associated proteins (SP-A, SP-B, SP-C, and SP-D). Its major function is to reduce surface tension at the air-water interface in the terminal airways by the formation of a surface-active film highly enriched in dipalmitoyl phosphatidylcholine (DPPC), thereby preventing alveolar collapse during expiration. SP-A and SP-D are large hydrophilic proteins, which play an important role in host defense, whereas the small hydrophobic peptides SP-B and SP-C interact with DPPC to generate and maintain a surface-active film. Surfactant replacement therapy with bovine and porcine lung surfactant extracts, which contain only polar lipids and SP-B and SP-C, has revolutionized the clinical management of premature infants with respiratory distress syndrome. Newer surfactant preparations will probably be based on SP-B and SP-C, produced by recombinant technology or peptide synthesis, and reconstituted with selected synthetic lipids. The development of peptide analogues of SP-B and SP-C offers the possibility to study their molecular mechanism of action and will allow the design of surfactant formulations for specific pulmonary diseases and better quality control. This review describes the hydrophobic peptide analogues developed thus far and their potential for use in a new generation of synthetic surfactant preparations.
Walther
F J
FJ
Harbor-UCLA Research and Education Institute, Torrance, California 90502, USA. fwalther@ucla.edu
Gordon
L M
LM
Zasadzinski
J A
JA
Sherman
M A
MA
Waring
A J
AJ
D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D015195:Drug Design; D006801:Humans; D007231:Infant, Newborn; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011510:Proteolipids / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology; D011663:Pulmonary Surfactants / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology; D012127:Respiratory Distress Syndrome, Newborn / Q000188:drug therapy
D011510:Proteolipids; D011663:Pulmonary Surfactants