Derivatives of Guanosine Triphosphate with Ribose 2′‐Hydroxyl Substituents

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Abstract
The preparation of 4 methylated and phosphorylated derivatives of GTP, 2''-O-methylguanosine 5''-triphosphate (PPP-Me2''Guo), guanosine 2''-monophosphate 5''-triphosphate (PPP-Guo-2''P), 3''-O-methylguanosine 5''-triphosphate (PPP-Me3''Guo) and guanosine 3''-monophosphate 5''-triphosphate (PPP-Guo-3''P), is described. These compounds were compared to GTP in their ability to support reactions catalyzed by E. coli initiation factor 2 (IF-2), elongation factor (EF), Tu and EF-G. As with previously studied GTP analogs, the nucleotide specificites of IF-2-dependent N-formylmethionylpuromycin formation and EF-Tu-dependent Ac-Phe2[N-acetylphenylphenyl]-tRNA formation were similar. There was little difference between the reactions supported by GTP, PPP-Me2''Guo, PPP-Me3''Guo and PPP-Guo-3''P, but PPP-Guo-2''P was a poor substrate with both enzymes. A spectrum of activity was observed in EF-G-dependent formation of N-acetylphenylalanylphenylalanylpuromycin. While PPP-Me2''Guo was almost as effective as GTP in supporting translocation, PPP-Guo-2''P was a very poor substrate, having even less activity than guanosine 3''-diphosphate 5''-triphosphate. Intermediate activities were observed with PPP-Me3''Guo and PPP-Guo-3''P, the former being more active than the latter.