Bioconjugation of Serum Albumin to a Maleimide‐appended Porphyrin/Cyclodextrin Supramolecular Complex as an Artificial Oxygen Carrier in the Bloodstream |
| |
Authors: | Dr. Hiroaki Kitagishi Hiroki Kawasaki Prof. Dr. Koji Kano |
| |
Affiliation: | Department of Molecular Chemistry and Biochemistry, Faculty of Science and Engineering, Doshisha University, Kyoto 610-0321, Japan |
| |
Abstract: | HemoCD is an inclusion complex of per‐O‐methylated β‐cyclodextrin dimer and an iron(II) porphyrin, which forms a stable O2 complex in water. Therefore, hemoCD has the potential for use as a synthetic O2 carrier in mammalian blood. In this study, a hemoCD derivative having a maleimide group (Mal‐hemoCD) was conjugated to a Cys residue of serum albumin via a Michael addition reaction in order to increase the circulation time of the O2 carrier. The O2‐binding affinities (P1/2 [Torr]) and half‐lives (t1/2 [h]) of the O2 adducts at pH 7.4 and 25 °C were determined to be 9 Torr and 23 h for Mal‐hemoCD, and 10 Torr and 14 h for albumin‐conjugated hemoCD (Alb‐hemoCD). Our pharmacokinetic study revealed that renal excretion of Alb‐hemoCD was effectively suppressed and that half of injected Alb‐hemoCD remained in blood at 3 h after injection. It is noteworthy that Mal‐hemoCD also had a long circulation time because of the bioconjugation reaction that occurred during circulation in the bloodstream. |
| |
Keywords: | cyclodextrins oxygen porphyrinoids protein modifications supramolecular chemistry |
|
|