Production and characterization of genetically modified human IL-11 variants

Emiko Sano*, Toshiaki Takei, Takuya Ueda, Kouhei Tsumoto

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)


Interleukin-11 (IL-11) has been expected as a drug on severe thrombocytopenia caused by myelo-suppressive chemotherapy. Whereas, development of IL-11 inhibitor is also expected for a treatment against IL-11 related cancer progression. Here, we will demonstrate the creation of various kinds of genetically modified hIL-11s. Modified vectors were constructed by introducing N- or O-glycosylation site on the region of hIL-11 that does not belong to the core α-helical motif based on the predicted secondary structure. N-terminal (N: between 22 to 23 aa), the first loop (M1:70 to 71 aa), the second loop (M2:114–115 aa), the third loop (M3:160–161 aa) and C-terminal (C: 200- aa) were selected for modification. A large scale production system was established and the characteristics of modified hIL-11s were evaluated. The structure was analyzed by amino acid sequence and composition analysis and CD-spectra. Glycan was assessed by monosaccharide composition analysis. Growth promoting activity and biological stability were analyzed by proliferation of T1165 cells. N-terminal modified proteins were well glycosylated and produced. Growth activity of 3NN with NASNASNAS sequence on N-terminal was about tenfold higher than wild type (WT). Structural and biological stabilities of 3NN were also better than WT and residence time in mouse blood was longer than WT. M1 variants lacked growth activity though they are well glycosylated and secondary structure is very stable. Both of 3NN and OM1 with AAATPAPG on M1 associated with hIL-11R strongly. These results indicate N-terminal and M1 variants will be expected for practical use as potent agonists or antagonists of hIL-11.

Original languageEnglish
Pages (from-to)205-217
Number of pages13
JournalBiochimica et Biophysica Acta - General Subjects
Issue number2
Publication statusPublished - 2017 Feb 1
Externally publishedYes


  • Agonist
  • Antagonist
  • Genetically modified hIL-11s
  • Glycosylated hIL-11s
  • Recombinant CHO cells
  • Structural stability

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology


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