Mimicking SP-C palmitoylation on a peptoid-based SP-B analogue markedly improves surface activity.
Hydrophobic lung surfactant proteins B and C (SP-B and SP-C) are critical for normal respiration in vertebrates, and each comprises specific structural attributes that enable the surface-tension-reducing ability of the lipid-protein mixture in lung surfactant. The difficulty in obtaining pure SP-B and SP-C on a large scale has hindered efforts to develop a non-animal-derived surfactant replacement therapy for respiratory distress. Although peptide-based SP-C mimics exhibit similar activity to the natural protein, helical peptide-based mimics of SP-B benefit from dimeric structures. To determine if in vitro surface activity improvements in a mixed lipid film could be garnered without creating a dimerized structural motif, a helical and cationic peptoid-based SP-B mimic was modified by SP-C-like N-terminus alkylation with octadecylamine. "Hybridized" mono- and dialkylated peptoids significantly decreased the maximum surface tension of the lipid film during cycling on the pulsating bubble surfactometer relative to the unalkylated variant. Peptoids were localized in the fluid phase of giant unilamellar vesicle lipid bilayers, as has been described for SP-B and SP-C. Using Langmuir-Wilhelmy surface balance epifluorescence imaging (FM) and atomic force microscopy (AFM), only lipid-alkylated peptoid films revealed micro- and nanostructures closely resembling films containing SP-B. AFM images of lipid-alkylated peptoid films showed gel condensed-phase domains surrounded by a distinct phase containing "nanosilo" structures believed to enhance re-spreading of submonolayer material. N-terminus alkylation may be a simple, effective method for increasing lipid affinity and surface activity of single-helix SP-B mimics.
Dohm
Michelle T
MT
Department of Chemistry, Northwestern University, Evanston, Illinois, 60208, USA.
Brown
Nathan J
NJ
Seurynck-Servoss
Shannon L
SL
Bernardino de la Serna
Jorge
J
Barron
Annelise E
AE
D002942:Circular Dichroism; D008051:Lipid Bilayers / Q000737:chemistry; D054878:Lipoylation; D018625:Microscopy, Atomic Force; D008856:Microscopy, Fluorescence; D037701:Pulmonary Surfactant-Associated Protein B / Q000737:chemistry*; D037721:Pulmonary Surfactant-Associated Protein C / Q000737:chemistry*; D013056:Spectrophotometry, Ultraviolet; D013499:Surface Properties; D013696:Temperature
D008051:Lipid Bilayers; D037701:Pulmonary Surfactant-Associated Protein B; D037721:Pulmonary Surfactant-Associated Protein C