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产生免疫原性的残基主要是位于蛋白表面的暴露残基,为了消除鼠抗体对人的免疫原性,利用表面再塑的方法对本室克隆的鼠抗人纤维蛋白抗体单链Fv片段进行了人源化分子设计.首先确定了鼠及人Fv片段的表面残基,在此基础上分析了鼠与人抗体Fv片段表面残基的差异,将存在差异的鼠抗体的表面残基换成人的,从而实现鼠抗体的人源化.提出了残基最高频率人源化及最相似链人源化两种分子设计方案.人源化的鼠抗人纤维蛋白抗体单链Fv片段的结构经Profiles-3D检测证明合理,替换的表面残基的溶剂可及性未变,而且未对CDRs的空间构象产生明显影响,应不会影响与纤维蛋白的亲和力,为鼠抗体人源化实验研究奠定了基础.
In order to eliminate the immunogenicity of the murine antibody to human, the immunogenicity residues were mainly exposed residues on the surface of the protein. The mouse anti-human fibrin antibody single-chain Fv fragment cloned in this chamber was subjected to the surface remodeling Humanized molecular design. Firstly, the surface residues of mouse and human Fv fragments were determined. Based on the analysis, the differences of the residues on the surface of Fv fragments between murine and human antibodies were analyzed. Humanized. Proposed the highest frequency of human residue and the most similar humanized chain two kinds of molecular design. The structure of the humanized murine anti-human fibrin antibody single-chain Fv fragment proved to be reasonable by Profiles-3D assays with unchanged solvent accessibility of the replaced surface residues without significant effect on the spatial conformation of the CDRs and should not Will affect the affinity with the fibrin, which lays the foundation for the humanized experiment research of the mouse antibody.