Sites of alkylation of poly(U) by agents of varying carcinogenicity and stability of products.
Several alkylating agents of widely varying reported carcinogenicity (dimethylsulfate, diethylsulfate, ethylmethanesulfonate, methylnitrosourea, ethylnitrosourea and ethylnitrosoguanidine) were reacted with poly(U) at pH values ranging from 4.5 to 7.5. All nucleophilic centers (internal phosphate groups, ribose hydroxyls, and O2, N-3 and O4 sites of the uracil base) were found reactive, though to different extents, at neutrality and in slightly acid solution. The distribution of products is a function of the alkylating agent and pH. The nitroso compounds are more reactive toward oxygens than are dialkylsulfates and alkylalkanesulfonates. The ratio of N : O alkyl products is strongly pH dependent, primarily due to the N-3 being most reactive at the higher pH values, while the diester is most reactive at the lower pH values. The extent of reaction of the O2, O4 or 2'-O or ribose is not greatly affected over the pH range tested. At pH 5.0 alkyl ribophosphotriesters mainly lose  alchol to re-form a stable phosphodiester. With increasing OH- concentration, the favored reaction is chain scission at the 3'-O-P bond.
D000477:Alkylating Agents; D000478:Alkylation; D002273:Carcinogens; D055598:Chemical Phenomena; D002621:Chemistry; D005020:Ethyl Methanesulfonate; D005038:Ethylnitrosourea; D006863:Hydrogen-Ion Concentration; D008745:Methylation; D008770:Methylnitrosourea; D008956:Models, Chemical; D009604:Nitrosoguanidines; D010756:Phosphoric Acids; D011072:Poly U; D012266:Ribose; D013464:Sulfuric Acids; D014529:Uridine
D000477:Alkylating Agents; D002273:Carcinogens; D009604:Nitrosoguanidines; D010756:Phosphoric Acids; D013464:Sulfuric Acids; D011072:Poly U; D012266:Ribose; D008770:Methylnitrosourea; D005020:Ethyl Methanesulfonate; D005038:Ethylnitrosourea; D014529:Uridine