Simple, helical peptoid analogs of lung surfactant protein B.
The helical, amphipathic surfactant protein, SP-B, is a critical element of pulmonary surfactant and hence is an important therapeutic molecule. However, it is difficult to isolate from natural sources in high purity. We have created and studied three different, nonnatural analogs of a bioactive SP-B fragment (SP-B(1-25)), using oligo-N-substituted glycines (peptoids) with simple, repetitive sequences designed to favor the formation of amphiphilic helices. For comparison, a peptide with a similar repetitive sequence previously shown to be a good SP mimic was also studied, along with SP-B(1-25) itself. Surface pressure-area isotherms, surfactant film phase morphology, and dynamic adsorption behavior all indicate that the peptoids are promising mimics of SP-B(1-25). The extent of biomimicry appears to correlate with peptoid helicity and lipophilicity. These biostable oligomers could serve in a synthetic surfactant replacement to treat respiratory distress syndrome.
Seurynck
Shannon L
SL
Department of Chemical and Biological Engineering, Northwestern University, 2145 Sheridan Road, Evanston, IL 60208, USA.
Patch
James A
JA
Barron
Annelise E
AE
D002942:Circular Dichroism; D015195:Drug Design; D008081:Liposomes / Q000737:chemistry; D018716:Molecular Mimicry; D015394:Molecular Structure; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry; D034444:Peptoids / Q000138:chemical synthesis / Q000737:chemistry*; D037701:Pulmonary Surfactant-Associated Protein B / Q000031:analogs & derivatives* / Q000737:chemistry*; D013050:Spectrometry, Fluorescence; D013499:Surface Properties; D013997:Time Factors; D014867:Water / Q000737:chemistry
D008081:Liposomes; D010455:Peptides; D034444:Peptoids; D037701:Pulmonary Surfactant-Associated Protein B; D014867:Water