Development of a biomimetic lung surfactant

Lyman Handy Colloquium SeriesPresentsAnnelise E. BarronAssociate Professor, Dept. of Bioengineering, Stanford University, Stanford, CA 94305AbstractWe are developing a new family of amphipathic peptide mimics for a synthetic lung surfactant (LS) replacement. Presently used exogenous LS replacements are extracted from animal lungs and used to treat respiratory distress sydrome in premature infants. The hydrophobic lung surfactant proteins SP-B and SP-C are necessary constituents of an effective surfactant replacement for the treatment of respiratory distress. As there are concerns and limitations associated with animal-derived surfactants, much recent work has focused on synthetic peptide analogues of SP-B and SP-C. However, creating an accurate peptide mimic of SP-C that retains good biophysical surface activity is challenging, given this lipopeptide's extreme hydrophobicity and propensity to misfold and aggregate. One approach that overcomes these difficulties is the use of helical poly-/N/-substituted glycines, or "peptoids," to mimic SP-C. We discuss advances in the design and characterization of peptoid-based SP-C mimics, which recently have led to the creation of our most biomimetic surfactant replacements to date.
Peptoid sequences were systemically varied in order to study surface activity effects of varying peptoid helicity,/ N/-terminal side chain chemistry and sequence length, as well as the side chain structures used within the hydrophobic C-terminal helix. The secondary structures of the peptoid SP-C mimics are analyzed in organic solution by CD spectroscopy. Langmuir-Wilhelmy surface balance experiments, epifluorescence videomicroscopy studies, and pulsating bubble surfactometry are used to characterize the surface activity and surface film morphology of the mimics in combination with a biomimetic phospholipid formulation. These results provide us with the first comprehensive structure-function relationships for peptoid-based analogues of surfactant protein C, as well as strong evidence that they offer significant promise for use in a synthetic replacement for animal-derived surfactants. There are several other potential applications for a safe and non-immunogenic surfactant formulation with these properties, other than treating respiratory distress, including protection against ventilator-induced lung injury, drug delivery to the lungs, and treatment of ear infections.

Location: Olin Hall of Engineering (OHE) - 122

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