Peptide inhibition of CCR3-mediated diseases or conditions
A C—C chemokine receptor 3 (CCR3) peptide analog that exhibits biased antagonism by binding to and inhibiting ligand-mediated signaling and chemotaxis while promoting the internalization and degradation of CCR3 is provided as is a method of using the peptide analog to treat, prevent, or ameliorate one or more symptoms of an eosinophil- or CCR3-mediated disease or condition.
1. A C—C chemokine receptor (CCR3) peptide analog comprising the amino acid sequence LLNLAISDLLFLVTLPFWIHY (SEQ ID NO:17) or LLFLVTLPFWIHYVRGHNWVFGH (SEQ ID NO:18), wherein said peptide analog is PEGylated and is up to 50 amino acid residues in length.
2. The CCR3 peptide analog of claim 1 , wherein the PEGylated peptide analog comprises between 5 and 50 polyethylene glycol units.
3. A pharmaceutical composition comprising the CCR3 peptide analog of claim 1 and a pharmaceutically acceptable carrier.
4. A metered dose inhaler comprising an aerosol canister equipped with a metered dose valve, wherein the aerosol canister is filled with a composition comprising one or more propellants and the CCR3 peptide analog of claim 1 .
5. A nanoparticle composition comprising the CCR3 peptide analog of claim 1 .
6. The nanoparticle composition of claim 5 , further comprising a second therapeutic agent.
7. A pharmaceutical composition comprising the nanoparticle composition of claim 5 and a pharmaceutically acceptable carrier.
8. A C—C chemokine receptor (CCR3) peptide analog comprising the amino acid sequence LLNLAISDLLFLVTLPFWIHY (SEQ ID NO:17) or LLFLVTLPFWIHYVRGHNWVFGH (SEQ ID NO:18), wherein said peptide analog is PEGylated and is up to 30 amino acid residues in length.
9. A C—C chemokine receptor 3 (CCR3) peptide analog comprising the amino acid sequence LLNLAISDLLFLVTLPFWIHYDDDC (SEQ ID NO:19) or LLFLVTLPFWIHYVRGHNWVFGHDDD (SEQ ID NO:20), wherein said peptide analog is PEGylated.
10. A C—C chemokine receptor 3 (CCR3) peptide analog comprising the amino acid sequence LLFLVTLPFWIHYVRGHNWVFGHDDD-(CH 2 CH 2 O) 27 —NH 2 (SEQ ID NO:21).