کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
9266242 1217274 2005 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Rational design of potent mimic peptide derived from monoclonal antibody: antibody mimic design
موضوعات مرتبط
علوم زیستی و بیوفناوری ایمنی شناسی و میکروب شناسی ایمونولوژی
پیش نمایش صفحه اول مقاله
Rational design of potent mimic peptide derived from monoclonal antibody: antibody mimic design
چکیده انگلیسی
The variable regions of antibody molecules bind antigens with high affinity and specificity. The binding sites are imparted largely to the hypervariable portions (i.e. CDRs) of the variable region. Peptides derived from antibody CDRs can bind antigen with similar specificity acted as mimic of antibody and become drug-designing core, although with markedly lower affinity. In this study, the 3D complex structure of tumor necrosis factor-alpha (TNFα) and its neutralizing monoclonal antibody Z12 was modeled using molecular docking method and optimized with molecular mechanism and dynamics method. The binding domains between TNFα and Z12 were determined theoretically and functional antigen epitopes were predicted. According to the 3D complex structure of TNFα and Z12, a novel antagonist peptide, named PT1, was designed theoretically. The experimental result showed that PT1 possessed significantly binding inhibition of TNFα to Z12 and protected L929 cells from the cytotoxic effect of TNFα. The designed mimic peptide was more amenable to synthetic chemistry and thus might be useful starting points for the design of smaller organic mimics.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Immunology Letters - Volume 98, Issue 2, 15 May 2005, Pages 311-316
نویسندگان
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