title: Neonatal Fc Receptor Binding Tolerance toward the Covalent Conjugation of Payloads to Cysteine 34 of Human Albumin Variants.
abstract: 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.
authors.affiliation: Interdisciplinary Nanoscience Center (iNANO), Aarhus University , DK-8000 Aarhus, Denmark.|Department of Molecular Biology and Genetics, Aarhus University , DK-8000 Aarhus, Denmark.
authors.forename: Steffan S
authors.initials: SS
authors.lastname: Petersen
authors.affiliation: Interdisciplinary Nanoscience Center (iNANO), Aarhus University , DK-8000 Aarhus, Denmark.|Department of Molecular Biology and Genetics, Aarhus University , DK-8000 Aarhus, Denmark.
authors.forename: Eva
authors.initials: E
authors.lastname: Kläning
authors.affiliation: Interdisciplinary Nanoscience Center (iNANO), Aarhus University , DK-8000 Aarhus, Denmark.|Department of Molecular Biology and Genetics, Aarhus University , DK-8000 Aarhus, Denmark.
authors.forename: Morten F
authors.initials: MF
authors.lastname: Ebbesen
authors.affiliation: Novozymes A/S , Krogshøjvej 36, DK-2880 Bagsværd, Denmark.
authors.forename: Birgitte
authors.initials: B
authors.lastname: Andersen
authors.affiliation: Novozymes Biopharma UK Ltd. , Castle Court, 59 Castle Boulevard, NG7 1FD Nottingham, United Kingdom.
authors.forename: Jason
authors.initials: J
authors.lastname: Cameron
authors.affiliation: Department of Molecular Biology and Genetics, Aarhus University , DK-8000 Aarhus, Denmark.
authors.forename: Esben S
authors.initials: ES
authors.lastname: Sørensen
authors.affiliation: Interdisciplinary Nanoscience Center (iNANO), Aarhus University , DK-8000 Aarhus, Denmark.|Department of Molecular Biology and Genetics, Aarhus University , DK-8000 Aarhus, Denmark.
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Howard
mesh_terms: D001667:Binding, Competitive; D003545:Cysteine / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D016503:Drug Delivery Systems; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D011108:Polymers / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D011961:Receptors, Fc / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism*; D012709:Serum Albumin / Q000235:genetics / Q000378:metabolism*
chemical_list: D015395:Histocompatibility Antigens Class I; D011108:Polymers; D011961:Receptors, Fc; D011993:Recombinant Fusion Proteins; D012709:Serum Albumin; D003545:Cysteine; C100688:Fc receptor, neonatal
keywords: albumin; biolayer interferometry; covalent conjugation; cysteine 34; neonatal Fc receptor (FcRn); poly(ethylene glycol)