Albumin-Oxanorbornadiene Conjugates Formed ex Vivo for the Extended Circulation of Hydrophilic Cargo

ACS Chem Biol. 2016 Aug 19;11(8):2320-7. doi: 10.1021/acschembio.6b00444. Epub 2016 Jun 27.

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.

MeSH terms

  • Animals
  • Camphanes / chemical synthesis
  • Camphanes / chemistry*
  • Camphanes / pharmacokinetics
  • Hydrophobic and Hydrophilic Interactions
  • Rats
  • Serum Albumin / chemistry*

Substances

  • Camphanes
  • Serum Albumin