Abstract
Human serum albumin (HSA) is a versatile protein found at high concentration in blood plasma and binds a range of insoluble endogenous and exogenous compounds. We have shown that complexation of functional molecules into HSA creates unique proteins never seen in nature. Complexing an iron-protoporphyrin IX into a genetically engineered heme pocket of recombinant HSA (rHSA) generates an artificial hemoprotein, which binds O2 reversibly in much the same way as hemoglobin. A pair of site-specific mutations, (i) introduction of a proximal histidine at the Ile-142 position and (ii) substitution of Tyr-161 with Phe or Leu, allows the heme to bind O2. Additional modification on the distal side of the heme pocket provides rHSA(triple mutant)-heme complexes with a variety of O2 binding affinity. Complexing a carboxy-C60-fullerene (CF) into HSA generates a protein photosensitizer for photodynamic cancer therapy. Energy transfer occurs from a photoexcited triplet-state of HSA-CF (HSA-3CF*) to O2, forming singlet oxygen (1O2). This protein does not show dark cytotoxicity, but induceds cell death under visible light irradiation.
