Hydrophobic homopolymeric peptides enhance the biophysical activity of synthetic lung phospholipids.

The effects of homopolymeric amino acids (molecular weight 2300 to 14,000) on the surface activity of dipalmitoyl phosphatidylcholine (DPPC) and DPPC/egg-phosphatidylglycerol (PG) were characterized by adsorption and dynamic surface tension lowering measurements at 37 degrees C. Homopolyamino acids studied included poly-L-leucine (poly-Leu) and poly-L-valine (poly-Val), since Leu and Val are known to be prominent in the structure of hydrophobic lung surfactant apoprotein SP-B and SP-C. In addition, several other homopolyamino acids with varying hydrophobicity index were also investigated, including poly-L-phenylalanine (poly-Phe), poly-L-serine (poly-Ser), poly-L-lysine (poly-Lys) and poly-L-glutamic acid (poly-Glu). Results showed that hydrophobic poly-Leu and poly-Phe at 1 and 10 weight percent greatly increased the adsorption facility of DPPC and DPPC/PG mixtures, with maximum surface pressures (up to 49 mN/m) near the equilibrium limit for phospholipid systems. In oscillating bubble studies, 1% mixture of poly-Leu or poly-Phe with DPPC or 8:2 DPPC/PG lowered surface tension into the range (near 1 mN/m) associated with active lung surfactant. In contrast, mixtures of DPPC and DPPC/PG with the more hydrophilic peptides poly-Ser, poly-Lys and poly-Glu showed little or no enhancement of surface activity over the phospholipids alone. Mixtures of poly-Val and phospholipids did not combine well with the simple co-sonication procedure used, and also exhibited little improvement in surface activity.(ABSTRACT TRUNCATED AT 250 WORDS)