Peptides which inhibit adhesion between leukocytes and endothelial cells
AssigneeThe Rockefeller University
InventorsElaine Tuomanen, H. Robert Masure
Life of this patent
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Abstract
Peptides which will inhibit the reaction between the RGD tripeptide of FHA and the integrin receptors of endothelial cells and their utility as therapeutic agents are described.
Claims8
A peptide which inhibits adhesion between leukocytes and endothelial cells, said peptide being selected from the group consisting of:
- IGALKAGAVEAASPRRARRALRQDFFTPGSVVVRAQGNVTVGRGDP (SEQ ID NO:
- 31),
- RQDFFTPGSVVVRAQGNVTVTRGDPMQGVLAQGDIIMDAKGGTLL (SEQ ID NO:
- 5),
- RGDPMQGVLAQGDIIMDAKGGTLLLRNDALTEMGTVTISADSAVL (SEQ ID NO:
- 6),
- RGDPHQGVLAQGDIIMDAKG (SEQ ID NO:
- 23),
- ETKEVDG (SEQ ID NO:
- 7),
- GRTRG (SEQ ID NO:
- 8),
- GLIQGRSVKVD (SEQ ID NO:
- 9),
- LGYQAIC (SEQ ID NO:
- 10), and
- LEHSTIESKISQSVLAAKGDKGKPAVSUKVAKKLFLNGTLRAVND (SEQ ID NO:
- 11).
A peptide which inhibits adhesion between bacteria and ciliated respiratory epithelial cells, said peptide selected from the group consisting of:
- AKKLFLNGTLRAVNDNNETMSGRQIDVVDGRPQITDAVTGEARKD (SEQ ID NO:
- 12),
- GRPQITDAVTGEARKDESVVSDAALVADGGPIVVEAGELVSHAGGIG (SEQ ID NO:
- 32), and
- IVVEAGELVSHAGGIGNGRNKENGASVTVRTTGNLVNKGYISHG (SEQ ID NO:
- 33).
A therapeutic composition useful for preventing adherence of Bordetella pertussis to ciliated respiratory epithelial cells in mammals comprising a peptide selected from the group consisting of:
- LEHSTIESKISQSVLAAKGDKGKPAVSUKVAKKLFLNGTLRAVND (SEQ ID NO:
- 11),
- AKKLFLNGTLRAVNDNNETMSGRQIDVVDGRPQITDAVTGEARKD (SEQID NO:
- 12),
- GRPQITDAVTGEARKDESVVSDAALVADGGPIVVEAGELVSHAGGIG (SEQ ID NO:
- 32),
- IVVEAGELVSHAGGIGNGRNKENGASVTVRTTGNLVNKGYISHG (SEQ ID NO:
- 33),
- PMQGVLAQGDIIMDAKGGTLLLRNDALT (SEQ ID NO:
- 34), and
- PMQGVLAQGDIIMDAKGGTLLLRNDALTEMSTVTISADSAVL (SEQ ID NO:
- 35).
A therapeutic composition useful for inhibiting the influx of leukocytes into inflamed tissue comprising a peptide selected from the group consisting of:
- IGALKAGAVEAASPRRARRLRQDFFTPGSVVVRAQGNVTVGRGDP (SEQ ID NO:
- 31),
- RQDFFTPGSVVVRAQGNVTVTRGDPMQGVLAQGDIIMDAKGGTLL (SEQ ID NO:
- 21),
- RGDPMQGVLAQGDIIMDAKGGTLLLRNDALTEMGTVTISADSAVL (SEQ ID NO:
- 22),
- LEHSTIESKISQSVLAAKGDKGKPAVSUKVAKKLPLNGTLRAVND (SEQ ID NO:
- 11),
- GRTRG (SEQ ID NO:
- 8),
- ETKEVDG (SEQ ID NO:
- 7),
- GLIQGRSVICVD (SEQ ID NO:
- 9), and
- LGYQAK (SEQ ID NO:
- 10).
An immunogenic composition comprising a peptide selected from the group consisting of:
- LEHSTIESKISQSVLAAKGDKGKPAVSUKVAKKLFLNGTLRAVND (SEQ ID NO:
- 11),
- AKKLFLNGTLRAVNDNNETMSGRQIDVVDGRPQITDAVTGEARKD (SEQ ID NO:
- 12),
- GRPQITDAVTGEARKDESVVSDAALVADGGPIVVEAGELVSHAGGIG (SEQ ID NO:
- 32),
- IVVEAGELVSHAGGIGNGRNKENGASVTVRTTGNLVNKGYISHG (SEQ ID NO:
- 33),
- PMQGVLAQGDIIMDAKGGTLLLRNDALT (SEQ ID NO:
- 34), and
- PMQGVLAQGDIIMDAKGGTLLLRNDALTEMSTVTISADSAVL (SEQ ID NO:
- 35).
An immunogenic composition comprising a pharmaceutically acceptable carrier together with an immunogenic-effective amount of a polypeptide portion of Bordetella pertussis FHA containing no RGD region or containing an amino acid sequence altered in the RGD region, wherein the polypeptide portion, when provided to a host for immunization, elicits antibodies which do not cross-react with cerebral endothelial cells.
Dependencies are inferred from the claim text.