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Title: A novel BLyS antagonist peptide designed based on the 3-D complex structure of BCMA and BLyS

Journal Article · · Biochemical and Biophysical Research Communications
OSTI ID:20854404
 [1];  [2];  [2];  [2]
  1. Department of Molecular and Cellular Pharmacology, College of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072 (China) and Department of Molecular Immunology, Beijing Institute of Basic Medical Sciences, Beijing 100850 (China)
  2. Department of Molecular Immunology, Beijing Institute of Basic Medical Sciences, Beijing 100850 (China)

B lymphocyte stimulator (BLyS) is a member of tumor necrosis factor (TNF) family. Because of its roles in autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and Sjogren syndrome (SS), BLyS antagonists have been tested to treat SLE- and RA-like symptoms in mice and obtained optimistic results. So far, reported BLyS antagonists were mostly decoyed BLyS receptors or anti-BLyS antibodies. In this study, a novel BLyS antagonist peptide, PT, was designed based on the modeling 3-D complex structure of BCMA and BLyS. The interaction mode of PT with BLyS was analyzed theoretically. The results of competitive ELISA demonstrated that PT could inhibit the binding of BCMA-Fc and anti-BLyS antibody to BLyS in vitro. In addition, PT could partly block the proliferating activity of BLyS on mice splenocytes. The BLyS antagonizing activity of PT was significant (p < 0.05). This study highlights the possibility of using BLyS antagonist peptide to neutralize BLyS activity. Further optimization of PT with computer-guided molecular design method to enhance its biopotency may be useful in developing new BLyS antagonists to treat BLyS-related autoimmune diseases.

OSTI ID:
20854404
Journal Information:
Biochemical and Biophysical Research Communications, Vol. 346, Issue 4; Other Information: DOI: 10.1016/j.bbrc.2006.06.005; PII: S0006-291X(06)01288-5; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
Country of Publication:
United States
Language:
English

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