A DIETHER PHOSPHONOLIPID SURFACTANT ANALOG, DEPN-8, IS RESISTANT TO PHOSPHOLIPASE-C CLEAVAGE

Increased activities of phospholipase A(2) and C (PLC) have been obser ved in the bronchoalveolar lavages of patients with adult respiratory distress syndrome (ARDS). DL-alpha-Di-O-hexadecylphosphonocholine [(R) (S)-DEPN-8], a surfactant analog of superior surface activity to the m ajor lung surfactant phospholipid, dipalmitoylphosphatidylcholine (DPP C), is not a substrate for phospholipases A(1), A(2) and D, but is a s ubstrate for PLC. (R)(S)-DEPN-8 was found in vitro to undergo signific antly less PLC-catalyzed degradation as compared to DPPC. The results suggest that (R)(S)-DEPN-8 and structurally related analogs may be use ful as components of exogenous replacement surfactant formulations for the treatment of ARDS-related lung injuries.