Artificial surfactants based on analogues of SP-B and SP-C.
The hydrophobic proteins SP-B and SP-C are important components of natural surfactant preparations currently used in clinical practice, and physiologically active surfactants can be made from isolated SP-B and/or SP-C reconstituted with synthetic lipids. Efforts have been made to produce these polypeptides, or analogues with similarfunction, by organic synthesis or expression in heterologous systems. It is important to obtain proper folding of the synthetic peptides, as required for optimal interaction with the surfactant lipids. Another issue is to avoid loss of SP-C activity due to alpha-helix to beta-sheet transition. This latter problem can be circumvented by replacing the polyvaline stretch of SP-C with a polyleucine stretch containing a few lysines. Palmitoylation of cysteines or serines at positions 5 and 6 also seems important for the properties of SP-C. SP-B, which is too big a molecule to be easily produced by organic synthesis. apparently can be replaced in an artificial surfactant by a peptide capable of cross-linking phospholipid bilayers. The development of synthetic analogues of the surfacant proteins might make it possible to tailor artificial surfactants for specific therapeutic missions, for instance by enhancing resistance to inactivation by meconium, plasma proteins, or oxygen radicals or maximizing bacteriostatic effects.
Johansson
J
J
Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden. Jan.Johansson@mbb.ki.se
Curstedt
T
T
Robertson
B
B
D000818:Animals; D055592:Biophysical Phenomena; D001703:Biophysics; D015195:Drug Design; D006801:Humans; D010168:Palmitates / Q000737:chemistry; D017433:Protein Structure, Secondary; D011510:Proteolipids / Q000737:chemistry*; D011663:Pulmonary Surfactants / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013500:Surface Tension; D013501:Surface-Active Agents / Q000737:chemistry* / Q000494:pharmacology
D010168:Palmitates; D011510:Proteolipids; D011663:Pulmonary Surfactants; D013501:Surface-Active Agents