Inhibition of protein synthesis in cell-free systems by homocitrullylamino adenosine

Abstract

Homocitrullylamino adenosine inhibits the incorporation of Ii4Clamino acids into a hot acid-insoluble form in cell-free systems derived from Escherichia coli and rat liver.The concentration necessary for one-half maximal inhibition in the E. coli system is i.l. Io -4 M. Addition of the intact molecule is necessary for the maximum inhibition. The inhibition does not appear to involve the activation of the amino acids or their transfer to s-RNA, but rather exerts its effect, like puromycin, at the level involving the s-RNA ribosomal complex.

Inhibition of Protein Synthesis by Amicetin, a Nucleoside Antibiotic*

“…Thus, amicetin acts in a manner similar to puromycin, homocitrullylaminoadenosine, gougerotin, and Blasticidin S. None of these antibiotics affect the acti-1 Abbreviations used: ATP, adenosine triphosphate; GTP, guanosine triphosphate. vation of amino acids or their transfer to s-RNA, but instead they block peptide synthesis following aminoacyl-RNA formation (Yarmolinsky and de la Haba, 1959; Guarino et al, 1963; Clark and Gunther, 1963; Nathans, 1964;Yamaguchi et al, 1965). This does not imply, of course, that the mechanism of action of the antibiotic is the same as that of other aminoacyl nucleosides.…”

“…When cytosine is the base, the amino acids are linked to a 4-amino-4-deoxyhexopyranose moiety of the d configuration (Figure lc,d). Despite these differences, all of these antibiotics have been shown to interfere with protein synthesis (Yarmolinsky and De la Haba, 1959; Guarino et al, 1963; Clark and Gunther, 1963; Nathans, 1964;Yamaguchi et al, 1965).…”

N-Containing Compounds of Macromycetes

“…86,87 Antibiotics 112 and 113 from the same fungus inhibit aminoacyl-tRNA synthetases. 88,89 Successive purification of a crude extract of cultured Mi Huan Jun (Armillariella mellea) mycelia, followed by an assay of the effect on complete ischemia in mice, led to the isolation of AMG-1 114, an N 6 -substituted adenosine with cerebral protecting activity. 90 The first C-alkylated purine, 6-methylpurine 115, and its riboside 116 and also 117 were isolated from cultures of the mushroom Collybia maculata (Scheme 30).…”

“…Nebularine 109 is a highly toxic nucleoside. It exerts its toxicity by being a very potent inhibitor of adenosine deaminase. , Cordycepin 110 and 3‘-amino-3‘-deoxyadenosine 111 , isolated from the mushroom Cordyceps militaris , act as feedback inhibitors of purine nucleotide biosynthesis by inhibiting the phosphoribosylpyrophosphate amidotransferase. , Cordycepin 110 is also a chain terminator for the 3‘-end of the growing RNA chain. , Antibiotics 112 and 113 from the same fungus inhibit aminoacyl- t RNA synthetases. , Successive purification of a crude extract of cultured Mi Huan Jun ( Armillariella mellea ) mycelia, followed by an assay of the effect on complete ischemia in mice, led to the isolation of AMG-1 114 , an N 6 -substituted adenosine with cerebral protecting activity . The first C-alkylated purine, 6-methylpurine 115 , and its riboside 116 and also 117 were isolated from cultures of the mushroom Collybia maculata (Scheme ) .…”

Adaptability of nonnatural aromatic amino acids to the active center of the E. coli ribosomal A site

“…The inhibitory activity of puromytin analogs has been examined as a measure for the adaptability of amino acids to the active center of ribosomal A site. The analogs of aromatic amino acids, L-phenylalanine and L-tyrosine were most effective [6-81, and those with 0-benzyl+serine, S-benzyl-Lcysteine [7,8], L-homocitrulline [9] and L-lysine [lo] were moderately active, whereas the analogs of other amino acids were almost inactive. The optical configuration of the amino acids was also important since the D-phenylalanyl analog was far less active than the L-isomer [6].…”