The rational designed antagonist derived from the complex structure of interleukin-6 and its receptor affectively blocking interleukin-6 might be a promising treatment in multiple myeloma

Biochimie
Jiannan FengB Shen

Abstract

Human interleukin-6 is involved in the maintenance and progression of several diseases such as multiple myeloma (MM), rheumatoid arthritis, or osteoporosis. Our previous work demonstrated that an interleukin-6 antagonist peptide (named PT) possessed potential bioactivity to antagonize the function of hIL-6 and could efficiently induce the growth arrest and apoptosis of XG-7 and M1 cells in a dose-dependent manner. In this study, the theoretical interaction of the peptide PT with its receptor was analyzed further more with molecular docking and molecular dynamics methods. The theoretical studies showed that PT possessed very high affinity to interleukin-6R and offered a practical means of imposing long-term blockade of interleukin-6 activity in vivo. According to the theoretical results, the biological evaluation of PT was researched on two different cells models with more sensitive approaches: (1) The antagonist activity of PT was studied on the interleukin-6 dependent MM cells (XG-7) cultured with interleukin-6. In the other interleukin-6 dependent MM cells (SKO-007), they survived themselves by auto/paracrine without the exogenous interleukin-6, and also could be antagonized by PT. The therapeutic value of PT only limited on ...Continue Reading

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