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    • 2. 发明授权
    • Nucleic acids encoding ara h 3 polypeptides
    • 编码ara h 3多肽的核酸
    • US07485708B2
    • 2009-02-03
    • US10228806
    • 2002-08-26
    • A. Wesley Burks, Jr.Gary A. BannonHugh A. SampsonRicki M. HelmJ. Steven StanleyPatrick A. Rabjohn
    • A. Wesley Burks, Jr.Gary A. BannonHugh A. SampsonRicki M. HelmJ. Steven StanleyPatrick A. Rabjohn
    • C07H21/04
    • C07K14/415A01K2217/05A61K38/00Y10S530/806Y10S530/868
    • It has been determined that allergens, which are characterized by both humoral (IgE) and cellular (T cell) binding sites, can be modified to be less allergenic by modifying the IgE binding sites. The IgE binding sites can be converted to non-IgE binding sites by masking the site with a compound that prevents IgE binding or by altering as little as a single amino acid within the protein, most typically a hydrophobic residue towards the center of the IgE binding epitope, to eliminate IgE binding. The method allows the protein to be altered as minimally as possible, other than within the IgE-binding sites, while retaining the ability of the protein to activate T cells, and, in some embodiments by not significantly altering or decreasing IgG binding capacity. The examples use peanut allergens to demonstrate alteration of IgE binding sites. The critical amino acids within each of the IgE binding epitopes of the peanut protein that are important to immunoglobulin binding have been determined. Substitution of even a single amino acid within each of the epitopes led to loss of IgE binding. Although the epitopes shared no common amino acid sequence motif, the hydrophobic residues located in the center of the epitope appeared to be most critical to IgE binding.
    • 已经确定,通过改变IgE结合位点,可以将以体液(IgE)和细胞(T细胞)结合位点为特征的过敏原修饰为较不敏感。 通过用防止IgE结合的化合物掩蔽位点或通过改变蛋白质内的单个氨基酸,最通常的是向IgE结合中心的疏水性残基,将IgE结合位点转化为非IgE结合位点 表位,以消除IgE结合。 该方法允许尽可能最小化蛋白质,除了在IgE结合位点之内,同时保持蛋白质激活T细胞的能力,并且在一些实施方案中,不显着改变或降低IgG结合能力。 实施例使用花生过敏原来证明IgE结合位点的改变。 确定了对免疫球蛋白结合重要的花生蛋白的每个IgE结合表位内的关键氨基酸。 每个表位中甚至单个氨基酸的取代导致IgE结合的丧失。 尽管表位不具有共同的氨基酸序列基序,但位于该表位中心的疏水性残基似乎对IgE结合最为关键。