The present invention provides a new 18-residue homodimerized peptide,
designated PIP [59-67] dimer (SEQ ID NO: 1), which is a mutant of the
optimized anti-inflammatory peptide P-NT.II, the patent for which has
recently been filed [1]. P-NT.II has the potential to modulate both the
inflammatory and bone damaging components of rheumatoid arthritis, and
was originally designed on the basis of the primary structure of the
anti-inflammatory protein termed `Phospholipase Inhibitor from Python
(PIP)` [2]. Using solid phase chemistry, variants of P-NT.II were
designed and examined for inhibitory activity against secretory
phospholipase A2 (sPLA2), a key enzyme involved in the inflammatory
pathway, and matrix metalloproteinases (MMPs) that are involved in the
remodeling and degradation of the extracellular matrix in rheumatoid
arthritis (RA) and cancer. Among the family of mutants tested, the
dimerized peptide was found to be the most potent inhibitor against sPLA2
as well as the human recombinant MMP-1. This invention provides the
utility of the peptide analogue PIP [59-67] dimer as a potential
therapeutic agent for modulation of inflammatory diseases such as
rheumatoid arthritis, and cancer. This invention relates to all the
polypeptide analogues (SEQ ID NO: 1 to 3) and polynucleotides (SEQ ID NO:
4), and to the use of those polypeptides and polynucleotides, their
synthetic chemical analogues or variants that inhibit activity and
synthesis of sPLA2 and MMPs, in the diagnosis, study, prevention and
treatment of rheumatoid arthritis and/or cancer.