Principles of Selective Inactivation of a Viral Genome. Comparative Kinetic Study of Modification of the Viral RNA and Model Protein with Oligoaziridines

E. A. Tsvetkova and N. M. Nepomnyaschaya^*

Zelinskii Institute of Organic Chemistry, Russian Academy of Sciences, Leninskii pr. 47, Moscow, 117913 Russia; fax: (095) 932-9659; E-mail: nmnkro@dialup.ptt.ru

^* To whom correspondence should be addressed.

Received November 17, 2000; Revision received January 9, 2001

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Comparative kinetic analysis of inactivation of bacteriophage MS2 infectivity and aminoalkylation of a model protein (trypsin inhibitor) with oligoaziridines was performed in order to evaluate the selectivity of viral RNA modification with oligocationic reagents. The transition from ethyleneimine monomer to di-, tri-, and tetramer leads to a sharp increase in the rate constant of infectivity inactivation, whereas the rate constant of protein modification changes insignificantly. The selectivity coefficient of the phage RNA aminoalkylation relative to trypsin inhibitor modification increases in this series by more than an order of magnitude. This effect is probably associated with the strengthening of the reagent binding to the nucleic acid, which implies a reaction mechanism that involves the formation of a reactive intermediate. The latter might be an electrostatic complex of the oligocationic reagent and RNA, the only polyanion in the virion. A pronounced decrease in the rate constant of infectivity inactivation in the presence of multiply charged anions (in phosphate buffer) and a biogenic polyamine (spermine) favors this hypothesis. Increasing the reaction temperature increases the rate constant of infectivity inactivation and decreases selectivity of the viral RNA modification.

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KEY WORDS: infectivity inactivation, selectivity, ethyleneimines, MS2 phage, trypsin inhibitor, viruses

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