title: Albumin-Oxanorbornadiene Conjugates Formed ex Vivo for the Extended Circulation of Hydrophilic Cargo.
abstract: Oxanorbornadiene dicarboxylate (OND) reagents were explored for the purpose of binding and releasing chemical cargos from endogenous circulating serum albumins. ONDs bearing gadolinium chelates as model cargos exhibited variable conjugation efficiencies with albumin in rat subjects that are consistent with the observed reactivity of each linker and their observed stability toward serum hydrolases in vitro. The terminal elimination rate from circulation was dependent on the identity of the OND used, and increased circulation time of gadolinium cargo was achieved for linkers bearing electrophilic fragments designed to react with cysteine-34 of circulating serum albumin. This binding of and release from endogenous albumin highlights the potential of OND linkers in the context of optimizing the pharmacokinetic parameters of drugs or diagnostic agents.
authors.affiliation: School of Chemistry and Biochemistry, Georgia Institute of Technology , Atlanta, Georgia 30332-0400, United States.|Department of Chemistry, The Scripps Research Institute , 10550 North Torrey Pines Road, La Jolla, California 92037, United States.
authors.forename: Cody J
authors.initials: CJ
authors.lastname: Higginson
authors.affiliation: Department of Molecular Therapeutics, The Scripps Research Institute , Scripps Florida, 130 Scripps Way, Jupiter, Florida 33458, United States.
authors.forename: Marsha R
authors.initials: MR
authors.lastname: Eno
authors.affiliation: Department of Molecular Therapeutics, The Scripps Research Institute , Scripps Florida, 130 Scripps Way, Jupiter, Florida 33458, United States.
authors.forename: Susan
authors.initials: S
authors.lastname: Khan
authors.affiliation: Department of Molecular Therapeutics, The Scripps Research Institute , Scripps Florida, 130 Scripps Way, Jupiter, Florida 33458, United States.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Cameron
authors.affiliation: School of Chemistry and Biochemistry, Georgia Institute of Technology , Atlanta, Georgia 30332-0400, United States.|Department of Chemistry, The Scripps Research Institute , 10550 North Torrey Pines Road, La Jolla, California 92037, United States.
authors.forename: M G
authors.initials: MG
authors.lastname: Finn
mesh_terms: D000818:Animals; D001892:Camphanes / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D057927:Hydrophobic and Hydrophilic Interactions; D051381:Rats; D012709:Serum Albumin / Q000737:chemistry*
chemical_list: D001892:Camphanes; D012709:Serum Albumin