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Synthetic surfactan...
Synthetic surfactant protein analogues
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- Johansson, J (författare)
- Karolinska Institutet
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Gustafsson, M (författare)
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Palmblad, M (författare)
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Zaltash, S (författare)
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Robertson, B (författare)
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- Curstedt, T (författare)
- Karolinska Institutet
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(creator_code:org_t)
- 2004-11-17
- 1998
- Engelska.
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Ingår i: Biology of the neonate. - : S. Karger AG. - 0006-3126. ; 7474 Suppl 1, s. 9-14
- Relaterad länk:
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http://kipublication...
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https://doi.org/10.1...
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Abstract
Ämnesord
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- 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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