Helical Peptoid Mimics of Lung Surfactant Protein C

Wu, Cindy W.; Seurynck, Shannon L.; Lee, Ka Yee C.; Barron, Annelise E.

doi:10.1016/j.chembiol.2003.10.008

Cited by 83 publications

(72 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This peptoid adopts a stable helical secondary structure in aqueous and organic solvents. Furthermore, it improved the kinetics of lipid adsorption to the interface and reduced the degree of film compression required to reach the minimum surface tension during cycling in a pulsating bubble surfactometer when it was introduced into lipid mixtures at a 10% (w/w) ratio [146]. No data on the in vivo performance of these molecules has been published to date.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Synthetic Pulmonary Surfactant Preparations: New Developments and Future Trends

Mingarro¹,

Lukovic²,

Vilar³

et al. 2008

CMC

View full text Add to dashboard Cite

Pulmonary surfactant is a lipid-protein complex that coats the interior of the alveoli and enables the lungs to function properly. Upon its synthesis, lung surfactant adsorbs at the interface between the air and the hypophase, a capillary aqueous layer covering the alveoli. By lowering and modulating surface tension during breathing, lung surfactant reduces respiratory work of expansion, and stabilises alveoli against collapse during expiration.Pulmonary surfactant deficiency, or dysfunction, contributes to several respiratory pathologies, such as infant respiratory distress syndrome (IRDS) in premature neonates, and acute respiratory distress syndrome (ARDS) in children and adults. The main clinical exogenous surfactants currently in use to treat some of these pathologies are essentially organic extracts obtained from animal lungs. Although very efficient, natural surfactants bear serious defects: i) they could vary in composition from batch to batch; ii) their production involves relatively high costs, and sources are limited; and iii) they carry a potential risk of transmission of animal infectious agents and the possibility of immunological reaction. All these caveats justify the necessity for a highly controlled synthetic material.In the present review the efforts aimed at new surfactant development, including the modification of existing exogenous surfactants by adding molecules that can enhance their activity, and the progress achieved in the production of completely new preparations, are discussed. Pulmonary surfactant function and dysfunctionThe respiratory surface of lungs constitutes the largest area of the human body exposed to the environment. Efficient gas exchange requires a large enough surface to be continuously exposed to air while minimising the barriers for oxygen and carbon dioxide to diffuse between air and the blood compartment [1]. At the same time, a selection of combined defence mechanisms is required to help keep such an essentially exposed area sterile of potential pathogenic microorganisms. Pulmonary surfactant, a lipid-protein complex produced by the alveolar epithelium of lungs, has been optimised to coordinate two main activities through natural evolution. On the one hand, it stabilises the respiratory surface against physical forces, therefore minimising the work required to maintain the large respiratory surface open to air [2][3][4]. On the other hand, pulmonary surfactant contains elements responsible for establishing a primary innate antipathogenic barrier, essential to ensure an intrinsically low pathogen load in the absence of induced defence mechanisms [5]. Extensive research in the last few decades has revealed some of the molecular mechanisms involved in pulmonary surfactant action. However, the manner in which both the biophysical and defence activities are intermingled and coordinately modulated in the alveolar spaces is now only beginning to be envisioned.Pulmonary surfactant is composed of approximately 90% lipids and 8-10% proteins, although only around 5% ...

show abstract

mentioning

confidence: 99%

“…As for the case of SP-B, non-peptide (peptoids) analogues that mimic amino acid sequence patterning and conformation of SP-C have been designed [146]. This peptoid adopts a stable helical secondary structure in aqueous and organic solvents.…”

mentioning

confidence: 99%

Synthetic Pulmonary Surfactant Preparations: New Developments and Future Trends

Mingarro¹,

Lukovic²,

Vilar³

et al. 2008

CMC

View full text Add to dashboard Cite

show abstract

“…Recently, non-natural bioinspired structures based on poly-N -substituted glycines (peptoids) with ␣ -chiral side chains have been created to mimic both the SP-B fragment SP-B 1-25 [6] and the SP-C analogue SP-C(Leu) [7] . These non-natural molecules in a lipid mixture improve surface pressure-area isotherms, surfactant fi lm morphology and dynamic adsorption, and decrease minimum and maximum surface tension during cycling in the pulsating bubble surfactometer.…”

Section: Peptides In Surfactantsmentioning

confidence: 99%

New Synthetic Surfactant – How and When?

Curstedt¹,

Johansson²

2006

Neonatology

View full text Add to dashboard Cite

Animal-derived surfactant preparations are very effective in the treatment of premature infants with respiratory distress syndrome but they are expensive to produce and supplies are limited. In order to widen the indications for surfactant treatment there is a need for synthetic preparations, which can be produced in large quantities and at a reasonable cost. However, development of clinically active synthetic surfactants has turned out to be more complicated than initially anticipated. The hydrophobic surfactant proteins, SP-B and SP-C, which are involved in the adsorption of surface-active lipids to the air-liquid interface of the alveoli and increase alveolar stability, are either too big to synthesize, structurally complex or unstable in pure form. A new generation of synthetic surfactants containing simplified phospholipid mixtures and small amounts of peptides replacing the hydrophobic proteins is currently under development and will in the near future be introduced into the market. However, more trials need to be performed before any conclusions can be drawn about the effectiveness of these synthetic surfactants in relation to natural animal-derived preparations.

show abstract

“…Non-natural bioinspired structures that capture both the amino acid sequence patterning and the 3-dimensional folds of natural surfactant proteins have been proposed for replacement of the hydrophobic SP-B and -C [26,27] . One type of these polymers is poly-N-substituted glycines (peptoids) with ␣ -chiral side chains which adopt a stable, helical secondary structure in organic and aqueous solutions and are nearly resistant to enzymatic degradation.…”

Section: Synthetic Surfactants Based On Simplifi Ed Peptidesmentioning

confidence: 99%

“…One type of these polymers is poly-N-substituted glycines (peptoids) with ␣ -chiral side chains which adopt a stable, helical secondary structure in organic and aqueous solutions and are nearly resistant to enzymatic degradation. These peptoids have been created to mimic both the SP-B fragment SP-B 1-25 [26] and the SP-C analog SP-C(Leu) [27,28] . About 10% (w/w) of these non-natural molecules added to the lipid mixture DPPC:palmitoyloleoylphosphatidylglycerol:palmitic acid (68: 22: 9, by weight) improve surface pressure-area isoterms, surfactant fi lm morphology and dynamic adsorption and decrease minimum and maximum surface tension during cycling in the pulsating bubble surfactometer.…”

Section: Synthetic Surfactants Based On Simplifi Ed Peptidesmentioning

confidence: 99%

New Synthetic Surfactants – Basic Science

Curstedt

Johansson²

2005

Neonatology

View full text Add to dashboard Cite

The hydrophobic surfactant proteins, SP-B and SP-C, promote adsorption of surface-active lipids to the air-liquid interface of the alveoli and are essential for alveolar stability and gas exchange. Synthetic surfactant preparations must contain at least one of these hydrophobic proteins, or analogs thereof, to have optimal effects when administered into the airways of patients with lung diseases. However, development of clinically active artificial surfactants has turned out to be more complicated than initially anticipated since the native hydrophobic proteins are structurally complex or unstable in pure form. The proteins have been replaced by different analogs which have the right conformation without forming oligomers. Increased understanding of the surfactant proteins will hopefully lead to development of effective synthetic surfactants which can be produced in large quantities for treatment of a wide range of respiratory disorders. Furthermore, the lipid composition seems to be important, as well as a high lipid concentration in the suspension. For successful treatment of many respiratory diseases, it is also desirable that the synthetic surfactant resists inactivation by plasma components leaking into the alveoli.

show abstract

Helical Peptoid Mimics of Lung Surfactant Protein C

Cited by 83 publications

References 50 publications

Synthetic Pulmonary Surfactant Preparations: New Developments and Future Trends

Synthetic Pulmonary Surfactant Preparations: New Developments and Future Trends

New Synthetic Surfactant – How and When?

New Synthetic Surfactants – Basic Science

Contact Info

Product

Resources

About