A diether phosphonolipid surfactant analog, DEPN-8, is resistant to phospholipase-C cleavage.
Increased activities of phospholipase A2 and C (PLC) have been observed 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 major lung surfactant phospholipid, dipalmitoylphosphatidylcholine (DPPC), is not a substrate for phospholipases A1, A2 and D, but is a substrate for PLC. (R)(S)-DEPN-8 was found in vitro to undergo significantly less PLC-catalyzed degradation as compared to DPPC. The results suggest that (R)(S)-DEPN-8 and structurally related analogs may be useful as components of exogenous replacement surfactant formulations for the treatment of ARDS-related lung injuries.
Lin
W H
WH
Department of Chemistry, University of Connecticut, West Hartford, USA.
Cramer
S G
SG
Turcotte
J G
JG
Thrall
R S
RS
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000031:analogs & derivatives* / Q000737:chemistry; D000328:Adult; D006801:Humans; D006868:Hydrolysis; D066298:In Vitro Techniques; D010712:Phosphatidic Acids / Q000737:chemistry*; D011663:Pulmonary Surfactants / Q000737:chemistry*; D013053:Spectrophotometry; D010738:Type C Phospholipases / Q000494:pharmacology*
C095411:DEPN 8; D010712:Phosphatidic Acids; D011663:Pulmonary Surfactants; D015060:1,2-Dipalmitoylphosphatidylcholine; D010738:Type C Phospholipases