Molecular Pharmacology, Vol 2, 585-592, Copyright © 1966 by the American Society for Pharmacology and Experimental Therapeutics

Chemical Methylation of Synthetic Polynucleotides

¹ Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06510

Polynucleotides were methylated in aqueous solution at 25° with methyl methanesulfonate. The reactions followed second-order kinetics, with relative reactivity of bases decreasing in the order: guanine > cytosine > adenine > uracil. Light scattering and viscosity techniques showed no changes in physical structure of polyuridylic acid, indicating that no methylation of the phosphodiester bond had occurred. Both polyadenylic and polycytidylic acids showed a decrease in molecular dimensions at low levels of methylation, presumably resulting from protonation of the substituted bases. As reported previously, polyadenylic acid showed a tendency to aggregate, but there was no evidence for such aggregation with methylated polycytidylic acid.

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ACKNOWLEDGMENT This work was supported by Grant PRA-10 from the American Cancer Society and by Public Health Service Grant No. GM-12416 from the National Institute of General Medical Sciences.