Effects of hydrophobic helix length and side chain chemistry on biomimicry in peptoid analogues of SP-C.

The hydrophobic proteins of lung surfactant (LS), SP-B and SP-C, are critical constituents of an effective surfactant replacement therapy for the treatment of respiratory distress syndrome. Because of concerns and difficulties associated with animal-derived surfactants, recent investigations have focused on the creation of synthetic analogues of the LS proteins. However, creating an accurate mimic of SP-C that retains its biophysical surface activity is extraordinarily challenging given the lipopeptide's extreme hydrophobicity and propensity to misfold and aggregate.

Lipid composition greatly affects the in vitro surface activity of lung surfactant protein mimics.

A crucial aspect of developing a functional, biomimetic lung surfactant (LS) replacement is the selection of the synthetic lipid mixture and surfactant proteins (SPs) or suitable mimics thereof. Studies elucidating the roles of different lipids and surfactant proteins in natural LS have provided critical information necessary for the development of synthetic LS replacements that offer performance comparable to the natural material. In this study, the in vitro surface-active behaviors of peptide- and peptoid-based mimics of the lung surfactant proteins, SP-B and SP-C, were investigated using three different lipid formulations.

A threaded loop conformation adopted by a family of peptoid nonamers.

Non-natural polymers with well-defined three-dimensional folds offer considerable potential for engineering novel functions that are outside the scope of biological polymers. Here we describe a family of N-substituted glycine or "peptoid" nonamers that folds into an unusual "threaded loop" structure of exceptional thermal stability and conformational homogeneity in acetonitrile. The structure is chain-length-specific and relies on bulky, chiral side chains and chain-terminating functional groups for stability.

Optical monitoring of bubble size and shape in a pulsating bubble surfactometer.

The pulsating bubble surfactometer (PBS) is often used for in vitro characterization of exogenous lung surfactant replacements and lung surfactant components. However, the commercially available PBS is not able to dynamically track bubble size and shape. The PBS therefore does not account for bubble growth or elliptical bubble shape that frequently occur during device use.

Helical peptoid mimics of lung surfactant protein C.

Among the families of peptidomimetic foldamers under development as novel biomaterials and therapeutics, poly-N-substituted glycines (peptoids) with alpha-chiral side chains are of particular interest for their ability to adopt stable, helical secondary structure in organic and aqueous solution. Here, we show that a peptoid 22-mer with a biomimetic sequence of side chains and an amphipathic, helical secondary structure acts as an excellent mimic of surfactant protein C (SP-C), a small protein that plays an important role in surfactant replacement therapy for the treatment of neonatal respiratory distress syndrome. When integrated into a lipid film, the helical peptoid SP mimic captures the essential surface-active behaviors of the natural protein.

Structural and spectroscopic studies of peptoid oligomers with alpha-chiral aliphatic side chains.

Substantial progress has been made in the synthesis and characterization of various oligomeric molecules capable of autonomous folding to well-defined, repetitive secondary structures. It is now possible to investigate sequence-structure relationships and the driving forces for folding in these systems. Here, we present detailed analysis by X-ray crystallography, NMR, and circular dichroism (CD) of the helical structures formed by N-substituted glycine (or "peptoid") oligomers with alpha-chiral, aliphatic side chains.

Extreme stability of helices formed by water-soluble poly-N-substituted glycines (polypeptoids) with alpha-chiral side chains.

Poly-N-substituted glycines or "peptoids" are protease-stable peptide mimics. Although the peptoid backbone is achiral and lacks hydrogen-bond donors, substitution with alpha-chiral side chains can drive the formation of stable helices that give rise to intense CD spectra. To systematically study the solution properties and stability of water-soluble peptoid helices with alpha-chiral side chains, we have synthesized and characterized an amphipathic, 36-residue N-substituted glycine oligomer.