鼠源单克隆抗体HAb25可变区的CDR-移植法人源化计算机辅助设计

目前鼠源抗体人源化是克服其免疫原性的主要手段。在结构模建基础上的计算机分析为抗体人源化设计提供了必不可少的辅助。本设计首先对肝细胞癌特异性抗体HAb25可变区进行了同源模建,然后分析决定CDR初始构象的可能残基,包括正则结构关键残基、CDR可接触残基、界面残基、包埋残基,以及与免疫识别密切相关的表面残基,综合考虑并结合多重序列比较,参照人源化模板,提出了人源化替代的方案。

Computer-aid CDR-grafted humanization design of a murine McAb HAb25 variable region

At present, humanization is the principal solution to reduce or eliminate the immunogenecity of murine monoclonal antibodies. Computer-aided analysis based upon structure prediction has provided an indispensable help in designing. In the research, the steric structure of the variable region (H25V) of a human hepatocellular carcinoma (HCC) specific murine McAb, HAb25, is firstly predicted by Homology Modeling . Then the critical residues for the natural conformation of CDRs, including key residues for the CDRs' canonical structure, CDRs possibly contact residues in FR, residues lying in the interface, and buried residues are all figured out. The residues that exposed in the surface are also listed. Take all of these elements into consideration, the humanized version of H25V is proposed according to human templates by multiple sequences alignment.