Neonatal Fc Receptor Binding Tolerance toward the Covalent Conjugation of Payloads to Cysteine 34 of Human Albumin Variants
Neonatal Fc Receptor Binding Tolerance toward the Covalent Conjugation of Payloads to Cysteine 34 of Human Albumin Variants
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DOI：
10.1021/acs.molpharmaceut.5b00605
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发表时间：
2016-02-01
影响因子：
4.9
通讯作者：
Howard, Kenneth A.
中科院分区：
文献类型：
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作者：
Petersen, Steffan S.;Klaning, Eva;Howard, Kenneth A.
白蛋白与细胞循环新生儿 Fc 受体 (FcRn) 的相互作用促进了其较长的循环半衰期，可用于延长药物半衰期。然而，货物共价连接到半胱氨酸 34 后的 FcRn 接合效应尚未得到研究。使用聚乙二醇聚合物来研究货物分子量对重组野生型 (WT) 白蛋白和为增加 FcRn 结合而设计的白蛋白变体的人 FcRn 接合的影响。观察到所有缀合物的亲和力降低；然而，工程白蛋白保持了高于未修饰的野生型白蛋白的亲和力，这使其成为有吸引力的药物递送平台。
The long circulatory half-life of albumin facilitated by the interaction with the cellular recycling neonatal Fc receptor (FcRn) is utilized for drug half-life extension. FcRn engagement effects following covalent attachment of cargo to cysteine 34, however, have not been investigated. Poly(ethylene glycol) polymers were used to study the influence of cargo molecular weight on human FcRn engagement of recombinant wild type (WT) albumin and an albumin variant engineered for increased FcRn binding. Decreased affinity was observed for all conjugates; however, the engineered albumin maintained an affinity above that of unmodified wild type albumin that promotes it as an attractive drug delivery platform.