Conformationally stable analogs of the response selective c5a agonist ep67
AssigneeBoard of Regents of the University of Nebraska
InventorsSam D. Sanderson, Jonathan Vennerstrom
Life of this patent
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Abstract
Conformationally-stable peptide analogs of the response selective C5a agonist EP67 having the formula Tyr-Ser-Phe-Lys-Asp-Met-Xaa-(Xaa2)-(D-Ala)-Arg (SEQ ID NO:1), wherein Xaa is a modified proline residue or a residue substitution for proline, and Xaa2 is leucine or N-methyl leucine. The conformationally-stable peptides selectively bind and activate APCs without directly engaging/binding C5a receptor-bearing cells involved in pro-inflammatory activities of natural C5a. Compositions and methods of using the peptide analogs are also described.
Claims24
(canceled)
A conformationally-stable peptide analog of EP67, having the formula:
- (SEQ ID NO:
- 1)
- Tyr-Ser-Phe-Lys-Asp-Met-Xaa-(Xaa2)-(D-Ala)-Arg,
- wherein:
- Xaa is selected from the group consisting of:
- a) alanine;
- b) N-methylalanine;
- b) 2-aminoisobutyric acid;
- c) 3-aminoisobutyric acid;
- d) N-methylisoleucine;
- e) singly-substituted proline analogs at the 2, 3, 4, and/or 5 positions of the pyrrolidine side chain;
- f) doubly-substituted proline analogs at the 2, 3, 4, and/or 5 positions of the pyrrolidine side chain;
- g) pseudoproline analog:
- cysteine-derived thiazolidine, serine-derived oxazolidine, or threonine-derived oxazolidine;
- h) trifluoromethylated pseudoprolines;
- i) proline analog or homolog having a constrained conformation;
- j) trifluoromethylated azetidine 2-carboxylic acid;
- k) trifluoromethylated homoserine;
- l ) oxetanyl-containing peptidomimetic;
- m) N-aminoimidazolidin-2-one analog;
- and
- n) nonchiral pipecolic acid analog:
- and
- Xaa2 is leucine or N-methyl leucine, said peptide having selective C5a receptor binding activity.
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-19. (canceled)
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Dependencies are inferred from the claim text.