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|Title:||Peptides-containing liposomal surfactants|
|Abstract:||The present invention discloses useful surfactant molecules including polypeptides, proteins, and a variety of other organic molecules, as well as methods of making and using same. Surfactant compositions, including liposomal surfactant compositions, are also disclosed. In one preferred embodiment, a pulmonary surfactant composition comprises one or more pharmaceutically acceptable phospholipids admixed with a polypeptide comprising about 10 to 60 amino acid residues, wherein the polypeptide includes a sequence constituted by alternating groupings of charged amino acid residues and uncharged amino acid residues.|
|Inventor(s):||Cochrane; Charles G. (La Jolla, CA), Revak; Susan D. (San Diego, CA)|
|Assignee:||The Scripps Research Institute (La Jolla, CA)|
|Filing Date:||Jun 07, 1995|
|Claims:||1. A polypeptide comprising at least 10 amino acid residues and no more than 60 amino acid residues, said polypeptide represented by the formula (Z.sub.a J.sub.b).sub.c Z.sub.d, wherein: Z is an amino acid residue independently selected from the group consisting of R, D, E, and K; J is an .alpha.-aminoaliphatic carboxylic acid selected from the group consisting of .alpha.-aminobutanoic acid, .alpha.-aminopentanoic acid, .alpha.-amino-2-methylpropanoic acid and .alpha.-aminohexanoic acid; a is 1 to 5; b is 3 to 20; c is 1 to 10; d is 0 to 3, |
and wherein said polypeptide, when admixed with a pharmaceutically acceptable phospholipid, forms a pulmonary surfactant having a surfactant activity greater than the surfactant activity of the phospholipid alone.
2. A compound to claim 1 wherein said phospholipid is present in the range of 50-100 weight percent, in a polypeptide:phospholipid weight ratio in the range of 1:7 to 1:1,000.
3. A compound according to claim 1 wherein said phospholipid is selected from the group consisting of: 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (dipalmitoylphosphatidylcholine, DPPC); phosphatidyl glycerol (PG); and an admixture of DPPC and PG in a weight ratio of about 3:1.
4. A compound according to claim 1 further comprising palmitic acid, wherein said phospholipid comprises 50-90 weight percent and said palmitic acid comprises the remaining 10-50 weight percent of the lipid portion of said surfactant.
5. A liposomal surfactant composition prepared from a polypeptide comprising at least 10 amino acid residues and no more than 60 amino acid residues, said polypeptide including a sequence having alternating groupings of amino acid residues represented by the formula (Z.sub.a J.sub.b).sub.c Z.sub.d, wherein: Z is an amino acid residue independently selected from the group consisting of R, D, E, and K; J is an .alpha.-aminoaliphatic carboxylic acid selected from the group consisting of .alpha.-aminobutanoic acid, .alpha.-aminopentanoic acid, .alpha.-amino-2-methylpropanoic acid and .alpha.-aminohexanoic acid; is 1 to 5; b is 3 to 20; c is 1 to 10; and d is 0 to 3.
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