Quinones of Natural and Synthetic Origin Investigation of Structure-Function Relationships of Cytotoxic

A sulfhydryl-arylating quinone from the mushroom Agaricus bisporus, with an absorption maximum at 490 nm, was demonstrated to inhibit DNA polymerase a purified from calf thymus. The "490 quinone" could be generated through tyrosinase-mediated oxidation of y-i-glutaminyl4-hydroxybenzene or y-u-glutammyl-3,4-dihydroxybenzene. However, when y-L-glutaminyl-3,4-dihydroxybenzene was oxidized to y-L-glutaminyl-3,4-benzoquinone (GBQ) with sodium periodate, the product had an absorp tion maximum (Xmax)at 440 nm rather than at 490 nm and demonstrated notably less sulfhydryl reactivity than did the 490 quinone. These properties defined that the 490 quinone is not GBQ, as had been suggested previously, but a product of the oxidation of GBQ by tyrosinase. Additional quiñones with an Xmasat 440 nm, produced from the oxidation of the acetyl and benzoyl analogs of yL-glutaminyl-4-hydroxybenzene and y-L-glutaminyl-3,4dihydroxybenzene, demonstrated the necessity of the amino acid side chain in the genesis of a quinone with an x,Ii;ixat 490 nm. Quiñones with an Xm.lxnear 490 nm were obtained after oxidation of 2,4,5-trihydroxyphenylalanine and 2,4,5-trihydroxyphenylethylamine, but these were ex ceedingly weak sulfhydryl reagents. Thus, while the pre cise structure of the 490 quinone remains unknown, these studies distinguish it from GBQ and demonstrate that the sulfhydryl reactivity of the 490 quinone is much greater than that of model quiñones with similar spectral proper ties.