Synthetic surfactant protein analogues.
Surfactant preparations for the treatment of respiratory distress syndrome (RDS) that contain phospholipids and small amounts of the two hydrophobic proteins, SP-B and SP-C, are presently obtained from animal lungs. Since structural information about SP-B and SP-C is available, it appears possible to design analogues that can replace the native proteins in synthetic surfactants. SP-C contains a single helix, but analogues with the poly-Val sequence of the native molecule do not fold into a native-like alpha-helical conformation. However, replacement of all Val with Leu yields efficient folding into a helical structure and Leu-based SP-C analogues effectively accelerate spreading of surfactant lipids and exhibit some physiological activity in animal models of RDS. The inferior in vivo activity of synthetic surfactants containing SP-C only compared to that of surfactant preparations derived from natural sources may be caused by a lack of covalently linked palmitoyl groups in the analogues and/or absence of SP-B. SP-B is significantly larger than SP-C and has a tertiary fold of several amphipathic helices in a dimeric structure. A single simplified amphipathic helical peptide containing only Leu and Lys does not mimic the surface properties of SP-B in vitro. These circumstances make the design of SP-B analogues from solely structural considerations less likely to be successful than in the case of SP-C.
Johansson
J
J
Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
Gustafsson
M
M
Palmblad
M
M
Zaltash
S
S
Robertson
B
B
Curstedt
T
T
D015195:Drug Design; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D011510:Proteolipids / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D011663:Pulmonary Surfactants / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D012127:Respiratory Distress Syndrome, Newborn / Q000188:drug therapy
D011510:Proteolipids; D011663:Pulmonary Surfactants