Biochemical and Biophysical Research Communications
A novel BLyS antagonist peptide designed based on the 3-D complex structure of BCMA and BLyS
Section snippets
Materials and methods
Reagents. Recombinant BLyS and anti-BLyS monoclonal antibody B7 were prepared as previously described [15]. BCMA-Fc was produced in this laboratory (unpublished data).
A BLyS antagonist peptide design. The BCMA and BLyS coordinates were obtained from the Protein Data Bank (PDB code:1oqd (BCMA), 1kxg (BLyS)). Considered with structural complementary and electrostatic matching while BLyS and BCMA contacted each other, molecular surface character was analyzed using molecular graphics and Delphi
BLyS antagonist peptide designed logically based on key residues of BCMA
The interacting mode of BCMA and BLyS was evaluated and the important amino residues of BCMA/BLyS interaction were determined. Analysis of the Connolly surface complemented by individual amino acid characteristics in the binding pocket revealed noticeable interactions between BLyS and its receptor BCMA, that could be exploited for antagonist design. Dealing with structural matching and electrostatic complementary, the key residues were defined as active chemical groups for the starting point of
Discussion
Blocking BLyS activity by antagonists to treat SLE and RA has been tested in animal model. Administration of decoyed receptors of BLyS, TACI-Fc into SLE-like mice has been demonstrated to improve the symptoms and inhibit the disease development [6], [17]. TACI-Fc also significantly improves the symptoms of RA in animal model [18]. These observations suggest that BLyS may be a potential therapeutic target to treat autoimmune. In this paper, we designed a BLyS antagonist peptide PT, based on the
Acknowledgments
This study was supported by National Sciences Fund (No. 30490240) and “973” Fund (No. 2003CB515508) of China.
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The comparison of BLyS-binding peptides from phage display library and computer-aided design on BLyS-TACI interaction
2015, International ImmunopharmacologyCitation Excerpt :BLyS binding peptides are usually obtained by phage display, which is a well-established technology for identification of peptide binders to a variety of proteins [16,17]. Since the crystal structures of BLyS and its receptors are known, it is possible to design BLyS antagonist peptides by computer-aided drug design (CADD) [18,19]. In this study, the activity of BLyS binding peptides from phage display library and computer-aided modeling was compared.
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These authors contributed equally to this work.