O2 binding to human serum albumin incorporating iron porphyrin with a covalently linked methyl-L-histidine isomer

Bioconjugate Chemistry
Akito NakagawaEishun Tsuchida

Abstract

We describe the significant difference in the O2 binding affinities of human serum albumin (HSA) incorporating 5,10,15,20-tetrakis{alpha,alpha,alpha,alpha- o-(1'-methylcyclohexanamido)phenyl}porphinatoiron(II) with a covalently linked 1-methyl-L-histidine or 3-methyl-L-histidine [HSA-FeP(1-MHis), HSA-FeP(3-MHis)]. The HSA-FeP(3-MHis) showed an extraordinarily high O2 binding affinity ( P1/2 = 0.2 Torr, 25 degrees C, pH 7.4), which is close to those of relaxed-state hemoglobin and myoglobin. However, replacement of the 3-methyl-L-histidine moiety in FeP(3-MHis) by 1-methyl-L-histidine caused a 35-fold reduction in O2 affinity; the P 1/2 value of HSA-FeP(1-MHis) (22 Torr, 37 degrees C, pH 7.4) is almost identical to that of human red blood cells. Results of kinetic studies indicate that the low O2 binding affinity of FeP(1-MHis) is predominantly manifested in the high O2 dissociation rate constant. In a toluene solution, an identical relationship in the O2 binding property was similarly observed for FeP(1-MHis) and FeP(3-MHis). The axial Fe-N(1-MHis) coordination might be restrained by steric interaction between the 4-methylene group of the histidine and the porphyrin plane.

References

Feb 1, 1978·Proceedings of the National Academy of Sciences of the United States of America·J P CollmanK S Suslick
Mar 1, 1975·Proceedings of the National Academy of Sciences of the United States of America·C K Chang, T G Traylor
Nov 23, 2000·Bioconjugate Chemistry·T KomatsuE Tsuchida
Feb 12, 2004·Chemical Reviews·James P CollmanLei Fu

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Citations

Sep 12, 2009·Drug Metabolism and Pharmacokinetics·Teruyuki KomatsuXue Qu
Feb 12, 2009·Bioconjugate Chemistry·Eishun TsuchidaKoichi Kobayashi

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