Peptide inhibitors of LFA-1/ICAM-1 interaction
AssigneeScience & Technology Corporation @ UNM
InventorRichard S. Larson
Life of this patent
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Abstract
Cyclic peptides inhibit LFA-1 interaction with ICAM-1 and are useful in treatment of hematopoietic neoplasms and in adjunct therapy in prevention of retinoic acid syndrome and diseases involving emigration of leukocytes into organ tissue.
Claims30
A composition comprising a cyclic peptide inhibitor of LFA-1/ICAM-1 interaction, wherein the cyclic peptide has the amino acid sequence of SEQ ID NO:3, or a substitution of SEQ ID NO:3 wherein the 2nd amino acid is methionine, the 5th amino acid is proline, the 6th amino acid is asparagine, the 7th amino acid is leucine, or the 8th amino acid is arginine, or a conservative variant of any thereof.
A method of inhibiting in a subject the interaction between LFA-1 expressed on a leukocyte and ICAM-1 expressed on a second cell, comprising administering to said subject an effective amount of a composition comprising a cyclic peptide, wherein said cyclic peptide has the amino acid sequence of SEQ ID NO:3 or a conservative variant thereof.
A method of preventing retinoic acid syndrome in a subject receiving a retinoic acid, 9-cis-retinoic acid, or a synthetic retinoid that causes or is suspected of causing retinoic acid syndrome when administered to a subject, comprising administering to said subject an effective amount of a composition comprising a cyclic peptide, wherein said peptide has the amino acid sequence of SEQ ID NO:3 or a conservative variant thereof.
A method for inhibiting growth of leukemia cells comprising preventing an LFA-1/ICAM-1 interaction between said leukemia cells and bone marrow stromal cells, wherein said method comprises contacting said bone marrow stromal cells with a cyclic peptide inhibitor of said LFA-1/ICAM-1 interaction, and further wherein the amino acid sequence of said cyclic peptide inhibitor is not a fragment of the amino acid sequence of LFA-1 or ICAM-1.
A therapeutic package for dispensing to, or for use in dispensing to, a mammal being treated for a hematopoietic neoplastic disease, myocardial infarction, radiation injury, asthma, rheumatoid arthritis, or lymphoma metastasis, wherein said package contains in a unit dose, an amount of a cyclic peptide having the amino acid sequence of SEQ ID NO:3 or a conservative variant thereof, effective to inhibit an LFA-1/ICAM-1 interaction in said mammal when administered periodically.
A composition comprising a cyclic peptide inhibitor of LFA-1/ICAM-1 interaction, wherein said cyclic peptide has the amino acid sequence of SEQ ID NO:3.
A method of inhibiting emigration of leukocytes from blood into tissue in a subject comprising administering to said subject an amount of a cyclic peptide having the amino acid sequence of SEQ ID NO:3 or a conservative variant thereof, effective to inhibit an LFA-1/ICAM-1 interaction in said subject.
A method of screening a candidate compound for binding to ICAM-1 comprising:
- (a) contacting ICAM-1 with a peptide having the amino acid sequence of SEQ ID NO:3 or a conservative variant thereof, such that said peptide having the amino acid sequence of SEQ ID NO:3 or a conservative variant thereof, is bound to the ICAM-1:
- (b) contacting said ICAM-1 with said bound peptide having the amino acid sequence of SEQ ID NO:3 or a conservative variant thereof, with said candidate compound;
- and
- (c) quantifying displaced peptide having the amino acid sequence of SEQ ID NO:3 or a conservative variant thereof.
Dependencies are inferred from the claim text.