Engineering S-protein fragments of bovine ribonuclease A for targeted drug delivery
Engineering S-protein fragments of bovine ribonuclease A for targeted drug delivery
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DOI：
10.1016/s1046-5928(02)00546-6
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发表时间：
2002-12-01
影响因子：
1.6
通讯作者：
Backer, JM
中科院分区：
文献类型：
--
作者：
Backer, MV;Gaynutdinov, TI;Backer, JM
牛胰腺核糖核酸酶A的S-蛋白和S-肽片段之间的高亲和力相互作用最近已被用于构建靶向药物递送的分子载体。载体组装为药物载体缀合的S-蛋白与S-肽标记的靶向蛋白的复合物。为了避免药物载体与S蛋白的随机化学交联，我们构建了一个突变的16 - 124 aa的RNase A片段，其中（122）ala被半胱氨酸残基取代。在大肠杆菌中表达的突变体和相应的野生型片段仅在S-肽存在下重折叠成功能构象。在去除S-肽后，两个片段都保留了结合S-肽和S-肽标记蛋白的能力。突变体片段中的（122）cys残基可用于位点特异性缀合。(C)2002 Elsevier Science（美国）。All rights reserved.
High affinity interaction between S-protein and S-peptide fragments of bovine pancreatic RNase A has been recently used for construction of molecular vehicles for targeted drug delivery. The vehicle is assembled as a complex of drug carrier conjugated S-protein with S-peptide-tagged targeting protein. To avoid random chemical crosslinking of drug carriers to S-protein, we constructed a mutant 16-124aa fragment of RNase A in which (122)ala is replaced with a cysteine residue. The mutant and the corresponding wild type fragments expressed in Escherichia coli are refolded into functional conformations only in the presence of S-peptide. After the removal of S-peptide, both fragments retain the ability to bind S-peptide and S-peptide-tagged proteins. The (122)cys residue in the mutant fragment is available for site-specific conjugation. (C) 2002 Elsevier Science (USA). All rights reserved.