A modified version of human serum albumin that binds oxygen has been created marking a first step towards a new form of artificial blood.
A modified version of human serum albumin (HSA) that binds oxygen has been created by British and Japanese researchers. The work marks a first step towards a new form of artificial blood.
HSA is the most abundant plasma protein in human blood. It naturally binds with haem, an iron-containing porphyrin group that is a central component of haemoglobin, to produce a complex that can be oxidised. Chemists and structural biologists from Waseda University, Tokyo, and Imperial College London have developed a version of this HSA-haem complex that can reversibly bind oxygen, rather than react with it.
After studying the crystal structure of the complex, the researchers experimented with various different versions, which they produced by introducing modified plasmids into the yeast Pichia pastoris. They discovered that replacing a specific tyrosine residue in the HSA-haem complex with a hydrophobic amino acid such as leucine or phenylalanine and introducing histidine as a proximal base led to effective oxygen binding. This modified complex could reversibly bind oxygen with an affinity that was only one order of magnitude less than that of haemoglobin.
All the previous candidates for artificial blood have been based on haemoglobin and are liable to induce high blood pressure. This would not happen with an artificial blood based on the HSA-haem complex, say the researchers, because of an electrostatic repulsion between HSA and blood vessel walls.
Much work remains, admits Stephen Curry, reader in structural biology at Imperial. ’The lifetime of oxygen binding at the HSA-haem complex is still too short for practical use,’ he told Chemistry World. ’At present we are trying to engineer additional mutations in the protein in order to enhance the oxygen binding properties still further.’ Jon Evans
et alJ. Am. Chem. Soc. (DOI: 10.1021/ja054819u)