Human serum albumin hybrid incorporating tailed porphyrinatoiron(II) in the alpha,alpha,alpha,beta-conformer as an O2-binding site.
We have found that recombinant human serum albumin (HSA) incorporating tailed porphyrinatoiron(II) in the alpha,alpha,alpha,beta-conformer can reversibly bind and release O2 under physiological conditions (pH 7.3, 37 degrees C) like hemoglobin and myoglobin. beta-2-Methylimidazolyl-tailed porphyrinatoirons (6a, 6b) are synthesized via four steps from the atropisomers of tetrakis(o-aminophenyl)porphyrin. The stereochemistry of the alpha,alpha,alpha,beta-conformer has been determined by NMR spectroscopy. 6a and 6b form stable O2-adduct complexes in toluene solution at room temperature. The association rate constants of O2 are 3.1- and 1.9-fold lower than those of the corresponding alpha,alpha,alpha,alpha-conformers (1a, 1b), indicating that the three substituents (cyclohexanamide or pivalamide groups) are close to each other on the porphyrin platform and construct a narrow encumbrance around the O2-coordination site. Although 6a and 6b are incorporated into the hydrophobic domains of HSA to produce the albumin-heme hybrid, only HSA-6a can bind O2 in aqueous medium. The cyclohexanamide fences are necessary for the tailed porphyrinatoiron to form a stable O2-adduct complex under physiological conditions. The O2-binding affinity (P(1/2)) of HSA-6a is 45 Torr (37 degrees C), and the O2 transporting efficiency between lungs and muscle tissues in the human body is estimated to be identical to that of human red blood cells. The HSA-6a solution will become one of the most promising materials for red blood cell substitutes, which can be manufactured on an industrial scale.
Nakagawa
Akito
A
Advanced Research Institute for Science and Engineering, Waseda University, 3-4-1 Okubo, Shinjuku-ku, Tokyo 169-8555 Japan.
Komatsu
Teruyuki
T
Iizuka
Makoto
M
Tsuchida
Eishun
E
D001665:Binding Sites; D006420:Hemeproteins / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007093:Imidazoles / Q000737:chemistry; D008665:Metalloporphyrins / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D008968:Molecular Conformation; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism*; D012709:Serum Albumin / Q000737:chemistry / Q000378:metabolism*
D006420:Hemeproteins; D007093:Imidazoles; D008665:Metalloporphyrins; D012709:Serum Albumin; C513578:porphyrinatoiron(II); D010100:Oxygen; C032655:2-methylimidazole