DESIGN AND SYNTHESIS OF A BIOLOGICALLY ACTIVE ANTIBODY MIMIC BASED ON AN ANTIBODY-ANTIGEN CRYSTAL STRUCTURE
DESIGN AND SYNTHESIS OF A BIOLOGICALLY ACTIVE ANTIBODY MIMIC BASED ON AN ANTIBODY-ANTIGEN CRYSTAL STRUCTURE
复制标题
基于抗体-抗原晶体结构的生物活性抗体模拟物的设计与合成
DOI：
10.1021/ja00086a005
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发表时间：
1994
期刊：
影响因子：
--
通讯作者：
M. Itzstein
中科院分区：
文献类型：
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作者：
M. Smythe;M. Itzstein
我们已经使用N9唾液酸酶（抗原）-NC 41（抗体）复合物的晶体结构来设计模拟大分子抗体的结合功能的低分子量化合物。从能量精修的晶体复合物中分析了抗体与蛋白质抗原之间的识别成分。根据该分析，抗体结合表面上与抗原的活性位点环368-370直接接触的四个氨基酸残基已被鉴定为贡献了蛋白质的大部分结合能。设计的目标化合物是一种限制性环肽，模拟这些氨基酸的受体结合构象，已合成并发现其抑制N9唾液酸酶活性，Ki为1 × 10（-4）M。
We have used the crystal structure of an N9 sialidase (antigen)-NC41 (antibody) complex to design a low molecular weight compound that mimics the binding function of the macromolecular antibody. The components of recognition between the antibody and the protein antigen have been analyzed from the energy-refined crystal complex. From this analysis, four amino acid residues on the antibody binding surface, which make direct contact with the active-site loop 368-370 of the antigen, have been identified as contributing the majority of the binding energy of the protein. The designed target compound, a constrained cyclic peptide, which mimics the receptor-bound conformation of these amino acids, has been synthesized and found to inhibit N9 sialidase activity, with a K-i of 1 x 10(-4) M.