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Ligand Design for Specific MHC Class I Molecules on the Cell Surface
Biochemistry ( IF 2.9 ) Pub Date : 2020-11-30 , DOI: 10.1021/acs.biochem.0c00735
Xizheng Sun 1 , Reika Tokunaga 1 , Yoko Nagai 1 , Ryo Miyahara 1 , Akihiro Kishimura 1, 2, 3, 4 , Shigeru Kawakami 5 , Yoshiki Katayama 1, 2, 3, 4, 6 , Takeshi Mori 1, 2, 3
Affiliation  

We have validated that ligand peptides designed from antigen peptides could be used for targeting specific major histocompatibility complex class I (MHC-I) molecules on the cell surface. To design the ligand peptides, we used reported antigen peptides for each MHC-I molecule with high binding affinity. From the crystal structure of the peptide/MHC-I complexes, we determined a modifiable residue in the antigen peptides and replaced this residue with a lysine with an ε-amine group modified with functional molecules. The designed ligand peptides successfully bound to cells expressing the corresponding MHC-I molecules via exchange of peptides bound to MHC-I. We demonstrated that the peptide ligands could be used to transport a protein or a liposome to cells expressing the corresponding MHC-I. This strategy may be useful for targeted delivery to cells overexpressing MHC-I, which have been observed in autoimmune diseases.

中文翻译:

细胞表面特定MHC I类分子的配体设计

我们已经验证了从抗原肽设计的配体肽可用于靶向细胞表面上的特定的主要主要组织相容性复合物I类(MHC-1)分子。为了设计配体肽,我们对每个具有高结合亲和力的MHC-1分子使用了报道的抗原肽。从肽/ MHC-1复合物的晶体结构,我们确定了抗原肽中的可修饰残基,并用具有被功能分子修饰的ε-胺基的赖氨酸取代了该残基。设计的配体肽通过交换与MHC-1结合的肽而成功地与表达相应MHC-1分子的细胞结合。我们证明了肽配体可用于将蛋白质或脂质体转运至表达相应MHC-1的细胞。
更新日期:2020-12-15
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