Utilization of FPRL1 as a functional receptor by serum amyloid a (SAA)
OwnerJi Ming Wang, Joost J. Oppenheim +4inventors
InventorsJi Ming Wang, Joost J. Oppenheim, Shao-Bo Su, Wang Hua Gong, Ji-Liang Gao, Philip M. Murphy
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Abstract
The present invention relates to the discovery that serum amyloid A (SAA) is a ligand for the FPRL1 receptor. Disclosed herein, are novel biological tools for the study of SAA/FPRL1 complex assembly and prophylactics, therapeutics, and methods of use of the foregoing, which modulate the association of SAA with FPRL1 and thereby effect responses including, but not limited to, signal transduction, chemotaxis, leukocyte migration, immune system response, amyloidosis, inflammatory response, infection, organ rejection, arthritis, atherosclerosis, and neoplasia.
Claims28
An isolated complex comprising a peptide agent having a sequence that corresponds to Serum amyloid A (SAA) or a conservative variant or functional fragment thereof bound to a molecule of FPRL1.
A polypeptide fragment of SAA that inhibits assembly of an SAA/FPRL1 complex by interacting with a FPRL1 receptor.
A polypeptide fragment of FPRL1 that inhibits assembly of an SAA/FPRL1 complex by interacting with a FPRL1 receptor.
A method of identifying an agent that modulates the assembly of an SAA/FPRL1 complex comprising:
- providing a support having disposed thereon a molecule of SAA;
- contacting the support with a candidate agent in the presence of a molecule of FPRL1;
- detecting the presence or absence of an SAA/FPRL1 complex;
- and
- identifying the agent as a molecule that promotes assembly of the SAA/FPRL1 complex or inhibits assembly of the SAA/FPRL1 complex.
A method of modulating a cellular response in a subject comprising:
- identifying a subject in need of a peptide agent that modulates a SAA/FPRL1 complex;
- and
- administering to the subject an amount of the peptide agent sufficient to modulate a cellular response, wherein the peptide agent comprises a sequence that corresponds to Serum amyloid A (SAA) or FPRL1, or conservative variants or functional fragments thereof.
A method of modulating a cellular response in a subject comprising:
- administering to the subject an amount of a peptide agent having a sequence that corresponds to Serum amyloid A (SAA) or FPRL1 or conservative variants or functional fragments thereof sufficient to modulate a cellular response;
- and
- measuring the effect of the peptide agent as a ligand that interacts with a FPRL1 receptor.
A method of making a pharmaceutical product comprising:
- providing a peptide agent having a sequence corresponding to Serum amyloid A (SAA) or FPRL1, or conservative variants or functional fragments thereof;
- providing a cell having a molecule of FPRL1 that interacts with the peptide agent;
- contacting the peptide agent with the cell under conditions that allow the peptide agent to interact with the FPRL1 molecule on the cell;
- identifying the presence or absence of signal transduction generated in response to the interaction of the peptide agent with the FPRL1 molecule;
- and
- incorporating the peptide into the pharmaceutical product.
Dependencies are inferred from the claim text.