Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10596231 | Bioorganic & Medicinal Chemistry Letters | 2013 | 6 Pages |
Abstract
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.
Keywords
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Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
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,