Photochemically catalyzed reaction of ochratoxin A with D- and L-cysteine.
The photolysis (>300 nm) of ochratoxin A (OTA, N-[[(3R)-5-chloro-8-hydroxy-3-methyl-1-oxo-7-isochromanyl]carbonyl]-3-phenyl-L-alanine, 1) in the presence of excess (2 and 12 molar equiv) cysteine (CySH) has been investigated and found to yield sulfur adducts 5 and 6 that are characterized by liquid chromatography-mass spectrometry and 1H-NMR spectroscopy. The adduct 5 was ascribed to the Michael addition conjugate resulting from covalent attachment of CySH to the ochratoxin quinone (4) generated by photooxidation of OTA. This species was also formed by photolysis of a synthetic sample of the hydroquinone of OTA (ochratoxin hydroquinone, 3) in the presence of 12 equiv L-CySH. The conjugate 5 derived from photolysis of 3 with L-CySH was used for 1H-NMR analysis. The sulfur adduct 6 was the major species detected from covalent attachment of CySH to photoactivated OTA, and it resulted from direct displacement of the OTA Cl atom by CySH. The implications of the cysteinyl adducts to the in vivo toxicity of OTA are discussed, with particular emphasis given to conjugate 5, as products from the photooxidative pathway may be of relevance to the nephrotoxic properties of OTA.
Brow
Mark E
ME
Department of Chemistry, Wake Forest University, Winston-Salem, NC 27109-7486, USA.
Dai
Jian
J
Park
Gyungse
G
Wright
Marcus W
MW
Gillman
Ivan G
IG
Manderville
Richard A
RA
D002384:Catalysis; D002853:Chromatography, Liquid; D003545:Cysteine / Q000737:chemistry* / Q000528:radiation effects*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D015394:Molecular Structure; D009793:Ochratoxins / Q000737:chemistry* / Q000528:radiation effects*; D010084:Oxidation-Reduction; D010777:Photochemistry; D013053:Spectrophotometry
D009793:Ochratoxins; C025589:ochratoxin A; D003545:Cysteine