Polypeptoid pulmonary surfactants
AssigneeNorthwestern University
InventorsAnnelise E. Barron, Ronald N. Zuckermann, Cindy W. Wu
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Abstract
The present invention provides spreading agents based on sequence-specific oligomers comprising a peptoid, a peptide-peptoid chimera, a retropeptoid or a retro(peptoid-peptide) chimera, and methods for using the same, including for the treatment of respiratory distress of the lungs. The spreading agents are sequence-specific oligomers, including retrosequence-specific oligomers, based on a peptide backbone, that are designed as analogs of surfactant protein-B or surfactant protein-C.
Claims31
A non-natural heteropolymeric pulmonary spreading agent comprising at least one N-substituted glycine residue and at least one amino acid residue corresponding to a natural surfactant-associated protein, said protein selected from the group consisting of surfactant-associated protein B and surfactant-associated protein C.
A pulmonary surfactant composition comprising a non-natural heteropolymeric spreading agent having at least one N-substituted glycine residue and at least one amino acid residue corresponding to a natural surfactant associated protein, said protein selected from the group consisting of surfactant-associated protein B and surfactant-associated protein C;
- and a component selected from the group consisting of naturally-occurring phospholipid, non-natural analogs of said phospholipids, commercial surface-active agents and combinations thereof, said composition having physiological alveolar surface activity.
A method of using N-substituent to enhance conformational control of a surfactant-associated protein mimic compound, said method comprising preparing a surfactant-associated protein mimic composition having at least one glycine residue, said preparation providing N-substituent of said glycine residue sufficient to enhance helical conformation of said composition.
A method for controlling alveolar surface activity, said method comprising:
- preparing a pulmonary surfactant composition including a non-natural heteropolymeric spreading agent having at one N-substituted glycine residue, and a lipid admixture;
- and
- administering said composition in an amount sufficient to reduce alveolar surface tension.
A method of using N-substitution to enhance the solubility of a helical surfactant-associated protein mimic compound, said method comprising preparing a helical, monomeric surfactant-associated protein mimic compound having at least one glycine residue, said preparation providing N-substitution of said glycine residue sufficient to maintain said monomeric compound and increase the solubility of said compound.
A method of using a polypeptoid to affect alveolar surface tension during an inhalation/exhalation cycle, said method comprising:
- providing a polypeptoid component consistent of a plurality of N-substituted glycine residues;
- combining said polypeptoid component with a surface-active lipid admixture, said combination having biomimetic alveolar surface activity;
- and
- administering said polypeptoid/lipid combination in an amount sufficient to reduce alveolar surface tension.
A pulmonary surfactant composition, comprising:
- a non-natural heteropolymeric spreading agent having the one-letter code structure
- HN-X1X2PVHLKR(NX3)n-CONH2
- wherein X1 and X2 are selected from the group consisting of an F residue and a C-palmitoyl residue, wherein NX3 is an N-substituted polypeptoid with X3 selected from the group consisting of ssb and spe substituents, and wherein n is an integer from about 13-20;
- and
- a lipid admixture combined with said spreading agent.
A pulmonary surfactant composition, comprising:
- a non-natural heteropolymeric spreading agent having the three-letter code structure
- HN-X1X2ProNvalNpmNleuNlysNarg(NX3)n-CONH2
- wherein X1 and X2 are selected from the group consisting of Npm, Noc and Nhd substituted glycine residues, wherein NX3 is an N-substituted polypeptoid with X3 selected from the group consisting of spe and ssb substituents, and wherein n is an integer from about 13-20;
- and
- a lipid admixture combined with said spreading agent.
Dependencies are inferred from the claim text.