Structural and mutagenic approach to create human serum albumin-based oxygen carrier and photosensitizer.
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 O(2) 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 O(2). Additional modification on the distal side of the heme pocket provides rHSA(triple mutant)-heme complexes with a variety of O(2) binding affinity. Complexing a carboxy-C(60)-fullerene (CF) into HSA generates a protein photosensitizer for photodynamic cancer therapy. Energy transfer occurs from a photoexcited triplet-state of HSA-CF (HSA-(3)CF(*)) to O(2), forming singlet oxygen ((1)O(2)). This protein does not show dark cytotoxicity, but induceds cell death under visible light irradiation.
Komatsu
Teruyuki
T
Research Institute for Science and Engineering, Waseda University, Tokyo, Japan. teruyuki@waseda.jp
Nakagawa
Akito
A
Qu
Xue
X
D000418:Albumins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D006801:Humans; D009153:Mutagens / Q000494:pharmacology; D010100:Oxygen / Q000378:metabolism*; D020795:Photophobia; D011487:Protein Conformation; D012709:Serum Albumin / Q000737:chemistry / Q000235:genetics*
D000418:Albumins; D009153:Mutagens; D012709:Serum Albumin; D010100:Oxygen