Acylation of carcinogenic hydroxamic acids by carbamoyl phosphate to form reactive esters

Abstract

1. Acylation of 2-(N-hydroxyacetamido)fluorene and several other aromatic hydroxamic acids by carbamoyl phosphate was studied and compared with the acylating activity of acetyl-CoA. Acetyl phosphate was also studied. 2. The carbamoylation reaction had a pH optimum of 4.5. The reaction had a lag period of 1h and was then linear for 4h. This linearity ranged between 0.5mm- and 8mm-carbamoyl phosphate concentration. 3. At pH7.5, acetyl-CoA was the most powerful acylating agent. Acetyl phosphate was a weaker acylating agent than either of the others. 4. Among the various hydroxamic acids tested with acetyl-CoA and carbamoyl phosphate at pH.7.5, 2-(N-hydroxyacetamido)fluorene was the most reactive. On the other hand the less reactive N-hydroxy derivatives of 2-acetamidonaphthalene, 2-acetamidophenanthrene and 4-acetamidostilbene reacted severalfold more with carbamoyl phosphate than with acetyl-CoA. 5. It is suggested that carbamoylation of aromatic hydroxamic acids might be one of the final activation steps in carcinogenesis by these compounds.