Identification of inhibitors against interaction between pro-inflammatory sPLA2-IIA protein and integrin αvβ3

Long Ye, Tiffany Dickerson, Handeep Kaur, Yoko K. Takada, Masaaki Fujita, Ruiwu Liu, John M. Knapp, Kit S. Lam, Neil E. Schore, Mark J. Kurth, Yoshikazu Takada

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)


Increased concentrations of secreted phospholipase A2 type IIA (sPLA2-IIA), have been found in the synovial fluid of patients with rheumatoid arthritis. It has been shown that sPLA2-IIA specifically binds to integrin αvβ3, and initiates a signaling pathway that leads to cell proliferation and inflammation. Therefore, the interaction between integrin and sPLA2-IIA could be a potential therapeutic target for the treatment of proliferation or inflammation-related diseases. Two one-bead-one-compound peptide libraries were constructed and screened, and seven target hits were identified. Herein we report the identification, synthesis, and biological testing of two pyrazolylthiazole-tethered peptide hits and their analogs. Biological assays showed that these compounds were able to suppress the sPLA2-IIA-integrin interaction and sPLA2-IIA-induced migration of monocytic cells and that the blockade of the sPLA2-IIA-integrin binding was specific to sPLA2-IIA and not to the integrin.

Original languageEnglish
Pages (from-to)340-345
Number of pages6
JournalBioorganic and Medicinal Chemistry Letters
Issue number1
Publication statusPublished - Jan 1 2013
Externally publishedYes


  • Inflammation
  • Inhibition of protein-protein interaction
  • Integrin
  • sPLA2-IIA

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry
  • Biochemistry


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