| 1. |
- Johansson, J, et al.
(författare)
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Pulmonary surfactant: emerging protein analogues
- 1999
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Ingår i: BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy. - : Springer Science and Business Media LLC. - 1173-8804. ; 11:2, s. 71-77
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Tidskriftsartikel (refereegranskat)
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| 2. |
- Johansson, J, et al.
(författare)
-
Synthetic surfactant protein analogues
- 1998
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Ingår i: Biology of the neonate. - : S. Karger AG. - 0006-3126. ; 7474 Suppl 1, s. 9-14
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Tidskriftsartikel (refereegranskat)abstract
- 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 α-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.
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| 3. |
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