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 ph osphatidylcholine (DPPC), thereby preventing alveolar collapse during expir ation. SP-A and SP-D are large hydrophilic proteins, which play an importan t 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. Surfac tant replacement therapy with bovine and porcine lung surfactant extracts, which contain only polar lipids and SP-B and SP-C, has revolutionized the c linical management of premature infants with respiratory distress syndrome. Newer surfactant preparations will probably be based on SP-B and SP-C, pro duced by recombinant technology or peptide synthesis, and reconstituted wit h selected synthetic lipids. The development of peptide analogues of SP-B a nd SP-C offers the possibility to study their molecular mechanism of action and will allow the design of surfactant formulations for specific pulmonar y diseases and better quality control. This review describes the hydrophobi c peptide analogues developed thus far and their potential for use in a new generation of synthetic surfactant preparations. (C) 2000 Academic Press.