Derivatives of guanosine triphosphate with ribose 2'-hydroxyl substituents. Interactions with the protein synthetic enzymes of Escherichia coli.
This report describes the preparation of four methylated and phosphorylated derivatives of GTP, 2'-O-methylguanosine 5'-triphosphate (PPP-Me2' Guo), and 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). These compounds were compared to GTP in their ability to support reactions catalyzed by Escherichia coli initiation factor 2(IF-2), elongation factor Tu (EF-Tu), and elongation factor G )EF-G). As with previously studied GTP analogues, the nucleotide specificities of IF-2-dependent N-formylmethionylpuromycin formation and EF-Tu-dependent Ac-Phe2-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 nucleotide being more active than the latter.
D004926:Escherichia coli / Q000187:drug effects / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D007700:Kinetics; D010445:Peptide Elongation Factors; D010448:Peptide Initiation Factors; D014176:Protein Biosynthesis / Q000187:drug effects*; D013329:Structure-Activity Relationship
D010445:Peptide Elongation Factors; D010448:Peptide Initiation Factors; D006160:Guanosine Triphosphate