SYNTHETIC PEPTIDE VACCINE DESIGN - SYNTHESIS AND PROPERTIES OF A HIGH-DENSITY MULTIPLE ANTIGENIC PEPTIDE SYSTEM
SYNTHETIC PEPTIDE VACCINE DESIGN - SYNTHESIS AND PROPERTIES OF A HIGH-DENSITY MULTIPLE ANTIGENIC PEPTIDE SYSTEM
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DOI：
10.1073/pnas.85.15.5409
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发表时间：
1988-08-01
影响因子：
11.1
通讯作者：
TAM, JP
中科院分区：
文献类型：
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作者：
TAM, JP
描述了一种通过固相方法直接合成肽-抗原基质的方便且通用的方法。该方法被称为多抗原肽系统（MAP），它利用一个由少量连续水平（n）的三功能氨基酸作为核心基质和2n肽抗原的简单支架，形成最终Mr 10,000的高密度肽抗原的大分子。选择用于研究的 MAP 模型是八分支 MAP，由三个水平的赖氨酸和八个用于锚定肽抗原的氨基末端组成的核心矩阵组成。 MAP 含有核心基质和 9-16 个氨基酸的肽，通过固相方法一次性合成制备。六种不同的 MAP 在兔子和小鼠体内引发了特异性抗体，其中五种产生的抗体与其相应的天然蛋白质发生反应。在兔子中，与用共价锚定到匙孔血蓝蛋白作为载体的相同肽制备的血清相比，血清具有显着更高的抗体效价。因此，MAP 提供了一种通用的、但化学上明确的方法来制备具有预定和可重复结构的载体结合抗原，并且可能适合于生产疫苗。
A convenient and versatile approach to the direct synthesis of a peptide-antigen matrix by the solid-phase method is described. The approach is called the multiple antigen peptide system (MAP) and it utilizes a simple scaffolding of a low number of sequential levels (n) of a trifunctional amino acid as the core matrix and 2n peptide antigens to form a macromolecule with a high density of peptide antigens of final Mr 10,000. The MAP model chosen for stydy was an octabranching MAP consisting of a core matrix made up of three levels of lysine and eight amino terminals for anchoring peptide antigens. The MAP, containing both the core matrix and peptides of 9-16 amino acids, was prepared in a single synthesis by the solid-phase method. Six different MAPs elicited specific antibodies in rabbits and mice, of which five produced antibodies that reacted with their corresponding native proteins. In rabbits, the sera had a considerably higher titer of antibodies than sera prepared from the same peptides anchored covalently to keyhole limpet hemocyanin as carrier. Thus, the MAP provided a general, but chemically unambiguous, approach for the preparation of carrier-bound antigens of predetermined and reproducible structure and might be suitable for generating vaccines.