Methods for Identifying Cathepsin G-Related Peptides as Modulators of Formylpeptide Receptors
Description of Invention:
Available for licensing and commercial development are methods for identifying peptides of Cathepsin G (CaG), or active variants thereof, which modulate activities of the receptor for bacterial chemotactic formyl peptides (FPR), including chemotactic behavior. It provides methods of designing therapeutic approaches related to the host defense based on the interaction of CaG and FPR, as CaG binds to FPR to mediate the proinflammatory activities of CaG. The inventive aspects relate to the finding that CaG induces a more partial and selective effects upon activation of FPR to mediate a certain and more limited immunological activity than other agonists that are also capable of binding FPR. The limitations in the activity include not inducing calcium flux, having only a week activation of mitogen-activated protein kinases (MAPKs), and being able to activate certain types of atypical protein kinase C (PKC), such as PKCzeta, while not activating PKCalpha and PKCbeta. These limitations are advantageous in attempting to limit the response in mobilizing the phagocytic leukocyte infiltration to mediate the clearance and repair of damaged tissue while not amplifying the general inflammatory response, which may result in damage to healthy and normal tissue.
Applications:
Identification of peptides of Cathepsin G that activate certain types of atypical protein kinase C, such as PKCzeta, while not activating PKCalpha and PKCbeta, to limit the response in mobilizing the phagocytic leukocyte infiltration while not amplifying the general inflammatory response.
Patent Status:
DHHS Reference No. E-281-2003/2 --
U.S. Patent Application No. 11/154,744 filed 17 Jun 2005, entitled “Cathepsin G-Related Peptides as Modulators of Formylpeptide Receptors (FPR),” published as US 20060008891
Relevant Publication: R Sun et al. Identification of neutrophil granule protein cathepsin G as a novel chemotactic agonist for the G protein-coupled formyl peptide receptor. J Immunol. 2004 Jul 1;173(1):428-436. [PubMed abs]
Licensing Status: Available for non-exclusive or exclusive licensing.
For Additional Information Please Contact: Cristina Thalhammer-Reyero PhD MBA
NIH Office of Technology Transfer
6011 Executive Blvd, Suite 325
Rockville, MD 20852-3804
Phone: (301) 435-4507
Email: thalhamc@mail.nih.gov
Fax: (301) 402-0220
