Neonatal Fc Receptor Binding Tolerance toward the Covalent Conjugation of Payloads to Cysteine 34 of Human Albumin Variants

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• 作者：Steffan S. Petersen ; Eva Kl?ning ; Morten F. Ebbesen ; Birgitte Andersen ; Jason Cameron ; Esben S. S?rensen ; Kenneth A. Howard
• 刊名：Molecular Pharmaceutics
• 出版年：2016
• 出版时间：February 1, 2016
• 年：2016
• 卷：13
• 期：2
• 页码：677-682
• 全文大小：437K
• ISSN：1543-8392

文摘

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.