title: Alterations of the C-terminal end do not affect in vitro or in vivo activity of surfactant protein C analogs.
abstract: The secondary structure, orientation and hydrogen/deuterium exchange of SP-C33, a surfactant protein C analog, in 1,2-dipalmitoyl-sn-glycero-3-phosphocholine/egg phosphatidylglycerol (8:2, wt./wt.) bilayers, was studied by attenuated total reflection Fourier transform infrared spectroscopy. This showed a transmembrane α-helix, in which about 55% of the amide hydrogens do not exchange for up to 20 h. Moreover, C-terminally modified SP-C33, either truncated after position 30, or having the methionine at position 31 exchanged for either lysine or isoleucine, showed the same secondary structure and orientation. The different peptides, suspended in 1,2-dipalmitoyl-sn-glycero-3-phosphocholine/1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol 68:31 (wt./wt.), were tested for surfactant activity in vitro in a captive bubble surfactometer and in vivo in an animal model of respiratory distress syndrome using premature rabbit fetuses. All preparations showed similar surface activity in the captive bubble surfactometer. Also, in the rabbit model, all preparations performed equally well and significantly better than non-treated controls, both regarding tidal volumes and lung gas volumes. Thus, truncation or residue replacements in the C-terminal part of SP-C33 do not seem to affect membrane association or surfactant activity.
authors.affiliation: Department of Molecular Medicine and Surgery, Karolinska Institutet at Karolinska University Hospital Solna, S-171 76 Stockholm, Sweden. andreas.almlen@ki.se
authors.forename: Andreas
authors.initials: A
authors.lastname: Almlén
authors.forename: Guy
authors.initials: G
authors.lastname: Vandenbussche
authors.forename: Bim
authors.initials: B
authors.lastname: Linderholm
authors.forename: Marie
authors.initials: M
authors.lastname: Haegerstrand-Björkman
authors.forename: Jan
authors.initials: J
authors.lastname: Johansson
authors.forename: Tore
authors.initials: T
authors.lastname: Curstedt
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D000831:Animals, Newborn; D041961:Deuterium Exchange Measurement; D005260:Female; D005333:Fetus; D006801:Humans; D007231:Infant, Newborn; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D008969:Molecular Sequence Data; D010455:Peptides / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D010715:Phosphatidylglycerols / Q000737:chemistry / Q000378:metabolism*; D011247:Pregnancy; D047928:Premature Birth; D017433:Protein Structure, Secondary; D037721:Pulmonary Surfactant-Associated Protein C / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D011817:Rabbits; D012127:Respiratory Distress Syndrome, Newborn / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D017550:Spectroscopy, Fourier Transform Infrared; D013990:Tidal Volume / Q000502:physiology
chemical_list: D008051:Lipid Bilayers; D010455:Peptides; D010715:Phosphatidylglycerols; D037721:Pulmonary Surfactant-Associated Protein C; D015060:1,2-Dipalmitoylphosphatidylcholine