Title:A Comparison of Biological Activity of B Lymphocyte Stimulator (BLyS) Antagonist Peptibodies and the Elucidation of Possible BLyS Binding Sites
Volume: 23
Issue: 1
Author(s): Xiafei Hao, Yanfeng Zhu, Chang Zheng, Xuegang Fu, Jiannan Feng, Beifen Shen, Jing Wei and Jian Sun
Affiliation:
Keywords:
Autoimmune diseases, B cell maturation antigen (BCMA), BLyS, BLyS antagonists, computer-aided drug design,
peptibodies.
Abstract: B lymphocyte stimulator (BLyS) overexpression is associated with autoimmune
diseases such as rheumatoid arthritis and lupus. BLyS antagonists are new
effective therapeutic strategies that have been studied extensively. BLyS-binding peptides,
BC originated from computer-aided drug design (CADD), 814 selected from the phage display library, as well as
the 3-copy of BC (3-BC), were fused with human IgG1 Fc to constitute peptide-Fc fusion proteins, referred as peptibodies.
BP-Fc, a peptibody possessing the identical sequence as BC-Fc but a His tag, was also constructed. The biological activities
of these peptibodies were assessed by Enzyme-Linked Immuno Sorbent Assay (ELISA). Furthermore, the potential
interacting orientations of BP and 814 with BLyS were studied. At 100 g/ml, BC-Fc, BP-Fc, 814-Fc and 3-BC-Fc
could distinctly inhibit 64 %, 50 %, 73 % and 56 % of the interaction of B cell maturation antigen (BCMA) with BLyS respectively.
BP-Fc demonstrated 15 % higher binding ratio with BLyS than BC-Fc at 100 g/ml. However, 814-Fc displayed
at least 39 % higher BLyS-binding activity than BP-Fc at different concentrations. The binding capacity of 3-BCFc
was slightly superior to BC-Fc. In addition, 814 and BP shared the identical domain on the surface of BLyS which involves
in binding with BCMA, but owned the detached orientations. The discovery of possible locations of the BLyStargeted
peptides lays the foundation for the development of novel antagonists. Both BP-Fc and 3-BC-Fc fusion proteins
could bind to BLyS in a dose-dependent manner and inhibit BLyS biological activity significantly, which might act as
candidate agents for autoimmune disease therapy.
